B Y TTRNG I HC DC H NINGUYN TH THANH HOINH GI TC DNG GIM AU,CHNG VIM V C TNH CACH PHMTECAN TRNTHC NGHIMKHA LUN TT NGHIP DC SH NI - 2013B Y TTRNG I HC DC H NINGUYN TH THANH HOINH GI TC DNG GIM AU,CHNG VIM V C TNH CACH PHMTECAN TRNTHC NGHIMKHA LUN TT NGHIP DC SNgi hng dn:Ts. Th Nguyt QuNi thc hin:B mn Dc lc - trng i hcDc H NiH NI 2013LI CMNSau thi gian nghin cu, thi im hon thnh kha lun cng l lc ti xinphp c by t lng cm n chn thnh ca mnh n nhng ngi hng dn,du dt v gip ti c th hon thnh tt kha lun tt nghip ca mnh.Trc ht, ti xin c th hin lng knh trng v bit n su sc nht ti Ts. Th Nguyt Qu, ging vin b mn Dc lc. C va l ngi ch bo dy dcho ti kin thc trong hc tp, va sa cha cho ti nhng sai st, khuyt im cabn thn v cho ti nhng li khuyn qu gi trong cuc sng thc t, gip ti ttin bctiptrnconngphatrc. Mtlnna, tixindnhchongithy knh yu s bit n chn thnh nht ca mnh.Ti xin chn thnh cm n Ths. Nguyn Th Thu Hng gip v cho tirt nhiu li khuyn qu gi trong qu trnh ti thc hin v hon thnh kha lunny.Ti xin chn thnh cm n cc anh ch k thut vin ti b mn Dc lc tntnhhtr,giptirtnhiutrongqutrnhtinhnhccthnghimnghin cu.Tixinchnthnhcmn cc thycgiotrongb mn Dclc truyn th cho ti nhng kin thc b ch thng qua cc bi ging, to nhng iukin thun li cho ti c hc tp v nghin cu ti b mn.Ti xin trn trng cm n Ban gim hiu, phng o to v cc thy c giotrngihcDcHNi tomiiukinthunli,gip tisut5nm hc tp.Cui cng, ti xin by t s yu thng v bit n su sc ti gia nh v bbn, nhng ngi lun bn chm sc, ng vin v gip ti trong sut nhngnm thng cuc i.H ni, ngy 21 thng 05 nm 2013Sinh vin,Nguyn Th Thanh HoiMC LCSTT NI DUNG TRANGT VN 1Chng 1: TNG QUAN 31.1 Tng quan v vim 31.1.1 Khi nim vim 31.1.2 Nguyn nhn gy vim 31.1.3 Phn loi vim 41.1.4 Sinh l, c ch qu trnh vim 41.1.5 Cc thuc chng vim 71.1.6 Cc m hnh nghin cu tc dng chng vim ca thuc 91.2 Tng quan v au 111.2.1 nh ngha 111.2.2 C ch ca au 111.2.3 Nguyn nhn gy au 121.2.4 Phn loi au 121.2.5 Thuc gim au 141.2.6 Mt s m hnh nghin cu tc dng gim au ca thuc 141.3 Tng quan v i tng nghin cu 141.3.1 Ngun gc v c im ca tectoridin 141.3.4 Mt s nghin cu v tc dng sinh hc ca tectoridin v mt s dchchit t x can15Chng 2: I TNG & PHNG PHP NGHIN CU 182.1 i tng nghin cu 182.1.1 ng vt nghin cu 182.1.2 Dng c, ha cht nghin cu 182.2 Phng php nghin cu 192.2.1 Phng php nh gi tc dng gim au 192.2.2 Phng php nh gi tc dng chng vim cp 202.2.3 Phng php nh gi c tnh cp tnh 212.2.4 Phng php nh gi c tnh bn trng din 222.3 Phng php x l s liu 24Chng 3: KT QU V BN LUN 253.1 Kt qu nghin cu 253.1.1 Kt qu nh gi tc dng gim au 253.1.2 Kt qu nh gi tc dng chng vim 263.1.3 Kt qu nh gi c tnh cp tnh 273.2.4 Kt qu nh gi c tnh bn trng din 283.2 Bn lun 343.2.1 Bn lun v tc dng gim au ca Tecan 343.2.2 Bn lun v tc dng chng vim ca Tecan 353.2.3 Bn v c tnh ca Tecan 36Chng 4: KT LUN V KIN NGH 404.1 Kt lun 404.1.1 V tc dng gim au 404.1.2 V tc dng chng vim cp tnh 404.1.3 V c tnh cp tnh 404.1.4 V c tnh bn trng din 404.2 Kin ngh 40TI LIU THAM KHO 41DANH MC CC K HIU VIT TTADN Acid deoxyribo NucleicNSAIDs Non steroidal anti-inflammatory drugsTNF Tumor necrosis factor alphaPAF Platelet Activating FactorUV Ultra violet radiationDANH MC CC BNG V HNH VTT Tn bng/hnh v Trang1 Bng 3.1. S cn au qun ca chut ti cc thi im. 252 Bng 3.2. T l ph chn chut ti cc thi im. 263 Bng3.3. Cn nng ca ng vt th nghim. 284 Bng 3.4. nh hng ca Tecan trn cc thng s huyt hcHC, Hb v HCT ca chut thc nghim.295 Bng 3.5. nh hng ca Tecan trn s lng tiu cu v slng bch cu ca chut thc nghim.306 Bng 3.6. nh hng ca Tecan trn cng thc bch cu. 317 Bng 3.7. nh hng ca tectoridin n hot SGPT, SGOT 318 Bng 3.8. nh hng ca Tecan n nng cholesterol tonphn v protein ton phn.329 Bng 3.9. nh hng ca Tecan n thng s creatinin huytthanh ca chut thc nghim.3310 Hnh 1.2. Cu trc ha hc ca tectoridin. 1511 Hnh 3.1. S thy phn tectoridin thnh tectorigenin di tcng caacid HCl v vi khun Bacteriodes spercoris trongng rut ca ngi.341T VN Vimlqutrnhbnhlph bin,cnhiuyut c th cth gyvim, bt c c quan no v m no cng c th b vim. Vim va l mt phnngbo v cth chngliyut gybnh,valphn ngbnhl.Qutrnhvimgyratn thng,hoi t,ri lon chcnngc quanPhn ngvimvth gynhiu nhhngncth.Vimnngvcptnhgyaun,khinbnhnhngimngonming,mtng v nhhngxuntontrng. Vy nn, bn cnh vic iu tr nguyn nhn gy vim, cn phi iu trlmgimcctriuchngvimnhmcithinchtlngcucsngchobnhnhn [8].Hainhmthuckhngvimchnhhinnayangcs dngnhiulthucchngvimkhngsteroid (NSAIDs) vthucchngvimsteroid(glucocorticoid).C hainhmthucnyucnhngtcdngph thnggpnhgylotd dy,ttrng,xuthuyttiuhaS raicaccNSAID cch chiucyclooxygenase-2tngnhlmtgiiphpmitrongiutr vimnhngsaulnltrofecoxib,valdecoxibb cmluhnh do gy tng cc yu t nguy c tim mch [2]. V vy vic tm kim nhngloi thuc gim au, chng vim mi hiu qu v an ton hn vn l vn caY hc hin nay. Bn cnh vic pht minh nhng thuc tn dc mi, tm kimthucc ngungct thin nhinda trnkinhnghimiutr caY hc ctruyn cng lun c cc nh khoa hc o su nghin cu. Flavonoid l hpchtt nhin cbitnvicctcdngdclngchnhtcdng chng khi u, tc dng chng x va ng mch, chng vim, chng dng, chng oxy ha[5] Thn r loi X can (Belamcanda chinensis Lem.) chanhiuloiisoflavonoid nhirigenin, tectoridin,tectorigenin,belamcanidin,methylirisolidon, iristectorigininA[12]. Trongtecroridinphnlpt dchchit thn r X can c chng minh l c tc dng chng vim in vitro docch tnghpchthahctrunggiangyvimprostaglandinE2[31].Tuynhinchngtichatmthynghincunonhgitcdngchngvim2catectoridincngnhv tcdnggimauvctnhcatectoridin invivo. V vy, nghin cu c thc hin vi nhng mc tiu sau:- nhgitcdngchngvimcaTecantrnmhnhgyvimbnchn chut bng carageenin.- nhgitcdnggimaucaTecantrnmhnhgy auqunKostler.- nhgictnhcptnhvctnhbntrngdincaTecantrnthc nghim.3CHNG 1:TNG QUAN1.1. TNG QUAN V VIM1.1.1. Khi nim vimVimlmtphn ngkhngchiucamdob ccyut hahc,vtlhaysinhhctncng[8].Biuhinbnngoicavim davnimmc c Celcus m t t cch y 2000 nm vi 4 du hiu in hnh gm:Sng, nng, v au [28]. Vim va l mt phn ng bo v c th chng liyut gybnhvalphn ngbnhlvqutrnhvimgyratnthng,hoi t, ri lon chc nng c quanPhn ng vim c th xut hin vi nhiumc khc nhau thm ch rt nng n v nguy him n tnh mng [8].1.1.2. Nguyn nhn gy vimC th xp nguyn nhn gy vim thnh 2 nhm ln l nguyn nhn ngoisinh v nguyn nhn ni sinh [8]:1.1.2.1. Nguyn nhn ngoi sinhCc nguyn nhn ngoi sinh gy vim thng gp nh:- Tcnhnchc:T xystnh tichnthngnngucthgyph hy t bo v m, lm gii phng ra nhng cht gy vim ni sinh.- Tcnhnvtl:Nhit qucaohayquthplmthoihaprotidtbo gy tn thng enzym. Tia x (UV, tia X) do to ra cc gc oxy t do gyph hy mt s enzym oxy ha u dn n phn ng vim. Ngoi ra tia x cngy tn thng ADN ca t bo.- Tc nhn ha hc: Cc acid mnh, kim mnh v cc cht ha hc khcnhthuctr su,ccctgyhyhoit bohocphongb cchenzym trong c th.- Tcnhn sinhhc:Lnguynnhnph binnht, gmvirus, vikhun,k sinh trng n bo, a bo hay nm1.1.2.2. Nguyn nhn ni sinhThiuoxytich,hoit m,xuthuyt,rilonthnkinhdinhdng(tc mch) l cc nguyn nhn gy vim thng gp. Ngoi ra, vim c th do4phn ng kt hp gia khng nguyn khng th (nh khi vim cu thn, vimtrong hin tng Arthus).1.1.3. Phn loi vimC nhiu cch phn loi vim nh [8]:- Theo nguyn nhn gm vim nhim khun v vim v khun.- Theo v tr vim gm vim nng, vim su (bn ngoi v bn trong).- Theodchr vimgmvimthanhdch,vimthuyt,vimmtytheo dch vim.- Theo din bin gm vim cp v vim mn.- Theotnhchtvimgmvimchiuvkhngchiu.Vimchiudohuqu xucaphn ngmindch;cnlilvimkhngchiu.Hai loi ny ch khc nhau v c ch vim m khng khc v bn cht.1.1.4. Sinh l, c ch qu trnh vim1.1.4.1. Giai on vim cp tnhVimcp:Khithigiandinbinvimngn(vipht vingy)vccccimnhtitdch,dchtitchanhiuproteinhuyttngvnhiubch cu a nhn trung tnh. Trong giai on cp tnh ca vim, c ba bin ich yul:Rilontunhon,rilonchuynha,tnthngmvtngsinht bo.Trnthct, baqutrnhnyanxenvlinquanchtch nnhau [8]. S ri lon tun hon ti vim [8]:Rilontunhonti vimthngxyrasm,ngaykhiyut gyvim tc ng ln c th. Theo Conheim, c th quan st thy 4 hin tng carilontunhongm:Rilonvnmch,todchr vim,bchcuxuynmch v hin tng thc bo.Ri lon vn mch: Ngay khi yu t vim tc ng, ti vim ln lt ccc hin tng sau:Hin tng co mch: Xy ra rt sm v rt ngn. Co mch c tnh phn x,do thn kinh co mch hng phn lm cc tiu ng mch co li.5Hintngsunghuytngmch:Xyrangaysauhintngcomch,utindocch thnkinhvsaucduytrvphttrinbngcchth dch.Cch th dchchnhls giiphngccenzymt lysosomcatbocht,ccchttrunggian(nhhistamin,bradykinin,prostaglandin,leucotrien)t t bomastvbchcuhayccsnphmthotngthcbo ca bch cu (nh protease, ion H+, K+), cc cytokin, yu t hoi t khiu(TNF),interleukin1(IL-1),yut hothatiucu(PAF),cbitlsc mt ca nitric oxyd (NO) do NO synthetase ca cc t bo vim b hot ha,sinhra. giaionny,ngmchvitunhondnrng,tngc lulngln p lc mu n vim. vim c ti mt lng mu ln giu oxy phhpviyucunnglngcacct bothcbovs chuynhaikhca chng. Nh sung huyt ng mch, bch cu c cung cp oxy v glucose to ra nng lng dng cho qu trnh thot mch, di chuyn v thc bo, dovylmnhit ti vimtngln.Cctcnhngydnmch(histamin,bradykinin,prostaglandin)tchlilmtngtnhthmthnhmchvgythot dch ra ngoi lng mch [8].Histaminlchthahctrunggianctmthyutinlinquannqutrnhvim.Mcdcmts thuc cchtcnhtrnhvihistamin(ivnH1histaminreceptor)ctcdngtrongvimnh giaionu.Bradykininv5-hydroxytryptamin(serotonin,5-HT)cngcvaitrtrongvim,nhngchtikhngcachngch cp ngtrongmts vimnhtnh.Leucotrien(LT)thamgiagiaiontinvim,ccchtikhngLT-receptor c dng iu tr hen. Tng hp prostanoid tng r rt trong vim.Prostaglandin E2(PGE2)vprostacyclin(PGI2) lnhngprostanoid chnh linquan n phn ng vim, c tc dng tng lu lng mu t chc tn thng,tng tnh thm thnh mch v tng bch cu n t chc tn thng [14].Hintngsunghuyttnhmch: Khidnschv cbncctbocht, ccyutgyvim...(itngthcbo),qutrnhthcbobtuyu i, sung huyt ng mch gim dn v chuyn sang sung huyt tnh mch.6Biu hin bn ngoi vim thay i: Bt nng, ph ch yu do tng tnh thmnn cnggim,gimcmgicau,chuynsangaum doccchthahc trung gian v ion K+, H+tch li. Vai tr sinh l ca sung huyt tnh mchl dn sch vim, chun b cho qu trnh sa cha v c lp vim, ngn cns lan rng ca tc nhn gy bnh [8].Hin tng mu: Xy ra sau sung huyt tnh mch, nguyn nhn do thnkinh vn mch ca huyt qun b t lit v tc dng ca cc cht gin mch nhNO,ngthiccchthahctrunggiannh:Histamin,prostaglandin,leucotrienlmtngtnhthmthnhmchgythothuyttngrakhimchmunmcmucqunh.Nhngnguynnhnkhcgynnhintngnycth k nnhbchcubmvothnhmchcntr luthngdng mu, t bo ni mc mch mu hot ha v ph i cn tr s vn chuynmu, nc trn vo m k gy ph v chn p thnh mch, s hnh thnh huytkhi gy tc mch. Hin tng mu c vai tr c lp vim, lmyu t gybnh khng th lan rng, ng thi tng cng qu trnh sa cha [8].Hnhthnhdchvim:Dchvimlccsnphmxuttitti vim.Dchr vimxuthinngayt khisunghuytngmch.Dch vimhnhthnhdo3yut chnhl:Dotng p lcthytnh trongcc mchmuti vim,dotcngcaccchttrunggianhahclmtngtnhthmthnhmch, gin cc khe gia cc t bo ni m thnh mch gy thot protein v yut cuicngl dotngplcthmthu trong vim,huqu cas tchlicc ion v cc cht phn t nh nh K+, H+ [8].Bchcuxuynmch: Khitnhthmthnhmchtng,cs thotmch,muchychm,lcbchcurikhidngtrc,xuynmchvdichuynn vim[8].Bch cu thc bo: Sau khi tp chung n vim, bch cu s tip cn viitngthcbo,btgi vtiuhaitng.itngb thcbogmcc vi sinh vt v cc mnh t bo b phn hy ti vim. Hin tng thc boc vai tr dn sch vim, to iu kin cho qu trnh hi phc [8].7 Ri lon chuyn ha trong vimVimgyrilonchuynhaglucid,toranhiuacidlactic.Acidlactictch li trong vim, lm pH gim dn t ra vo trong trung tm vim. Vimnng c th gy nhim toan ton c th. Ri lon glucid mun gy tng chuynha ym kh ri lon chuyn ha lipid v protid [8]. Tn thng mThng c hai loi tn thng: Tn thng tin pht do nguyn nhn gyvim to ra v tn thng th pht do cc ri lon ti vim to nn [8]. Tng sinh t bo v qu trnh lm lnh vt thngVim bt u bng tn thng v kt thc bng qu trnh ti to. M x vccmchmumilcs hnhthnhsothayth chomtnthng,lmlnh vt thng [8].1.1.4.2. Giai on vim mn tnhVimmndin bin t vi ngynhng thngthmchn hngnm.V mhccs xmnhpcalymphobovithcbo,mctnthngngang bng vi mc sa cha tn thng.Giaionmntnhcaphn ngvimgmphn ngt bophttrinchmvs hnhthnhmtokeo.S dict bongungct muhocttrung m vn tip din vim rt lu sau s can thip ca yu t tn cng. vim c th din tin ti ch lm m hoc hoi t. S tng sinh nguyn bo siv tn to mao mch to thnh u ht. U ht khi tin trin, mt cc thnh phn tbo v cc mao mch ng thi m to keo xut hin dn dn [13].1.1.5. Cc thuc chng vimHinnaythucchngvimgmc2nhm: thucchngvimkhngsteroid (cc NSAID) v thuc chng vim steroid (cc glucocorticoid).1.1.5.1. Thuc chng vim khng steroid (NSAIDs) Cch chngvim: Ccthucchngvimkhngsteroidu cchenzymcyclooxygenase(COX),ngncntnghpprostaglandinlchttrunggianhahcgyvim,do lmgimqutrnhvim.Ngoi raNSAIDscn8i khng vi h enzym phn hy protein, ngn cn qu trnh bin i lm bnvng mng lysosom v i khng tc dng ca cc cht trung gian ha hc nhbradykinin,histamin,serotonin, cch ha ngngbchcu, cch s dichuyn ca bch cu ti vim [4][14].Mt s thuc thuc nhm NSAID nh: Aspirin, indomethacin, meloxicam,peroxicam,diclofenac,celecoxib,ibuprofen,nimesulid Ngoitcdngchng vim cc NSAID cn c tc dng h st v gim au [4][14]. Ch nhchung:Ccdngvimcpvmn(vimkhpdngthp,vim thp khp cp, vim ct sng dnh khp, bnh gout) [4]. Tcdngkhngmongmun:Ch yulinquann cch tnghpprostaglandin[4]. Trntiuhagykch ng,authngv,nnghncthlot d dy t trng, xut huyt tiu ha Trn mu gy ko di thi gian chymudo c ch kttptiucu,gimtiucuvgimprothrombin,huqugy ko di thi gian ng mu, mt mu khng nhn thy qua phn, tng nguycchymu. Trnthn,gimsclccuthn, nc,tngkalimu,vimthn kTrn h hp gy cn hen gi.Cc tc dng khng mong mun khc: Mn cm, gy c vi gan, d tt thai nhi nu dng thuc trong ba thng u ca thai k1.1.5.2. Thuc chng vim steroid (glucocorticoid)Glucocorticoidbaogmglucocorticoidt nhindovngbv thngthnsnxut ra(hydrocortisonvcortison)vglucocorticoidtnghpnhpredinisolon,methyprednisolon,triamcinolon,dexamethason...Ngoi raglucocorticoidcnctcdng cch mindch,chngd ng,tcngtrnqu trnh chuyn ha glucid, protid, lipid, chuyn ha mui nc [4]. Cch chngvim: Glucocorticoidctcdngchngvimldo cch phospholipase A2 thng qua kch thch tng hp lipocortin, lm gim tnghpc leucotrienvprostaglandin.Ngoirancnctcdng cch dngbch cu n nhn, a nhn, lympho bo i vo m gy khi pht phn ngvim. Thuc c tc dng chng vim do mi nguyn nhn [4].9 Ch nh trongiutr vim: iutr vimmid ng,myay,vimda tip xc, vim c, khp, vim da[4]. Chngch nh:Lotd dyttrng,mncmvithuc,nhimnm,virus, ang dng vaccin sng [4]. Tcdngkhngmongmun: Ph,tnghuytpdogi natrivnc;Lotd dy,ttrng;Vtthngchmlnso,d nhimtrng;Tngnghuythoclmnngthmbnhithong;Nhcc,teoc,mic;Longxng,xpxng,rilonphnb m,suythngthncpkhidngthuc t ngt[4].1.1.6. Cc m hnh nghin cu tc dng chng vim ca thucCnc voccgiaiontrongqutrnhvim,cth chia ccmhnhth nghimtcdngchngvimcamtthuc thnhhainhm,baogmccmhnhgyvimcpvbncp vccmhnhgyvimmn [29].Trong phm vi kha lun ny, chng ti ch tng quan v cc m hnh gy vimcp v bn cp.Cc m hnh gy vim cp v bn cp M hnh gy ph bn chn chut [13][22][28]:Nguyntctinhnh: Saukhitimvobnchnsaucachutcctcnhngyvimnhformaldehyd,dextrin,albumintrng,kaolin,sulfatpolysaccharid(carrageenin,naphthoyheparamin), ccchtnys kchhotphn ng vim, gy gin mch v tng tnh thm thnh mch. Kt qu ca qutrnh vim ny l hin tng ph bn chn chut. Cc thuc c tc dng chngvim s c kh nng c ch hin tng ph.Trongqutrnhgyvimbngcarragenin,mc vimtiatrongkhongthigian3-4gi,iviaerosilvkaolinthigiangyvimcthko di n 24 gi hay 2 ngy. Do cn la chn tc nhn gy vim ph hpvimcchnghincu,khngch theotcdngchngvimmnhhay yum cn ph thuc vo thi gian thuc c tc dng.10Ccch tiunhgi: Sosnhmc phchnchut cngthiimsau khi gy vim gia l ng vt c dng mu th v l chng nh gitc dng chng vim ca mu th.M hnh gy ph chn chut bng carragenin c s dng bi nhiu nhnghincuvcchngminhphhpvimcchsnglcnhgitcdngchngvimcathucchngvimkhngsteroid,steroid,thuckhnghistamin, khng serotonin.Mhnhgyph bnchnchutlmhnh ngin,d tinhnh vimcp p ng trong vi gi, thi gian tin hnh ngn. M hnh gy ban bng tia t ngoi chut lang [13][28]:Nguyntc:Mhnhgyban bngtiat ngoicWilhelmimtln u tin (1949), ng nhn thy kh nng lm chm s pht trin ca ban dotiat ngoicaphenylbutazonvccthucchngvimkhngsteroid.Nng prostaglandinEtngln trongsutthigian24gi saukhi dachuttipxcvitiacctmbcx 280-320nm. Ban lduhiuutincavim, khi phn ng vim cha i km vi ph n v tng tit dch.Ch tiu nh gi: nh gi mc vim bng cch o din tch ban .Phmvipdng: Phngphpnycth pdng nghincutcdng ca thuc chng vim steroid. M hnh gy ph tai chut bng oxazolon [22][28]:Nguyn tc: M hnh gy ph tai chut bng oxazolon c m t u tinbi Evans v cng s (1971) l m hnh da trn phn ng qu mn mun cac th gy ra bi oxazolon. Kt qu ca s phi nhim vi oxazolon l lm vmng t bo mast, gii phng ra cc cht trung gian gy ph.nh gi: Tnh t l % tng khi lng ca tai phi so vi tai tri ri tnhgi tr trung bnh t l % tng khi lng tai chut trong mi l. Sau tnh tl phn trm c ch ph ca l th so vi l chng.11Phmvipdng: Mhnhnychophp nhgikh nngchngvimtich cathuc.ycnglphngphpphhp nhgitcdngchng vim ca thuc chng vim steroid v khng steroid.u im: p dng cho c thuc chng vim khng steroid v steroid.Nhc im: Qu trnh tin hnh ko di, tn nhiu thi gian. M hnh o mc thm thu mch mu [22][28]:Nguyntc: Ccchttrunggianhahcgyvimnhlhistamin,prostaglandinv leucotriencgiiphngsaukhit bobchcumastbkch thch gy gin cc tiu ng mch, lm tng tnh thm mch mu. Kt qul dch v protein huyt tng thot ra gy ph. Nhng tc ng ny b c chbinhngthuckhnghistamin,thuc cch s chuynhacaacidarachidonic v thuc c ch th th ca leucotrien.nhgi: nhgitcdngchngtngtnhthmcathuc thngquanng cht nhum xanh Evans khi tim di da.Phmvipdng: Th nghimnycdng nhgitcdngcacc thuc chng li s thm thu mch mu gy ra bi cc cht gy vim.1.2. TNG QUAN V AU1.2.1. nh ngha:au l cm gic cc b c th t hi kh chu n d di khng chu ni.auldos kchthch voudythnkinhcmgicau,thngsauchnthng hoc bnh [9].au l c ch t v ca c th chng li nhng kch thchchi,cngckhiltriuchngbotrccamtbnhno.Tuynhin,c nhng trng hp au ch do xc cm, t k m th ca bnh nhn [9].1.2.2. C ch ca auTrndacnhiuutncngdythnkinhbitha(ccth th).Kchthch vonhngth th ny s dn n vic truyn cc tn hiu au n no.Ccth th c nhycmkhcnhau,mts ch phn ng khib kchthchmnhnhct,nhitnngtrnda,nhngloikhcphn ngvinhngkchthch va phi nh lc ca vt rn, ko dn hoc nhit cha gy bng.12Cng c th th au ti cc cu trc khc ngoi da, bao gm cc mch mu vgn. Phn ln cc c quan ni tng c t th th [9].1.2.3. Nguyn nhn gy auTc nhn gy au rt a dng: ha hc, vt l, c hc Cc tc nhn nykchthchvongn sicmgicv truynxungngv trung ng, bo chocth bitminguyhim rib nguynnhngyau.Ticcmb tnthng,ccchttrunggianhahc(bradykinin,kinin,prostaglandin,serotonin) tit ra li gp phn lm tng cm gic au., tng tc dn truyncm gic au v lm au nng thm [2].1.2.4.Phn loi au au thc th:Kch thch gy cm gic au thng r rng. au thng khu tr r, c thquichiucaunitng.Cmgicaugimnudngthucchngvimhoc thuc gim au gy ng [7]. au do bnh thn kinh:Khngcmtkchthchrrngnogy auc.authngkhngkhutrrrt.Cmgicauthtthng.Dngthucgimaugyng ch gimau mt phn [7].1.2.5. Thuc gim auThucgimauctcdnglmgimhocmtcmgicaumkhngtc dng ln nguyn nhn gy au, khng lm mt cm gic khc v khng lmmtthcCcthucgimaucphnbitvithucgyt,lchtngncns dntruynkchthchchit impdngnh thnkinhtrungng.Ccthucgimaucchialm2loi:Thucgimautrungng(thucgimaugyng)vthucgimaungoivi (khnggyng).Ngoira cn c thm nhm thuc h tr trong iu tr au [13].1.2.5.1. Thuc gim au trung ng C ch gim au: Cc thuc thuc nhm ny c tc dng gim au do cch trungtmau no vngncn dntruyncmgicaut tysngln13no. Tc dng gim au thng km tc dng gy ng v gy nghin [3]. Nhmny c phn lm 2 nhm theo mc gim au [2]:- Loi gim au mnh: Morphin, meperidin, fentanyl, methadon- Loi gim au trung bnh: Codein, tramadol, propoxyphen Ch nhtrongiutr au:Cctrnghpaunngnhgyxngi, au sau m, cn nhi mu c tim, ung th giai on cui[3] Tcdngkhngmongmun:Gytobn,bunnnvnn, cch hhp, gy nghin, hi chng kch thch, tt huyt p [3]1.2.5.2. Thuc gim au ngoi viMts thucthucnhm gimaungoivinh:Aspirin,diclofenac,indomethacin, ibuprofen, naproxen[2] Cch gimaucaccNSAID: Ccthucgimaungoivi cchCOXdo cch s tnghp prostaglandin,chttrunggianhahckhiphtnhiuqutrnhsinhlvbnhlcacth.Prostaglandins khimochovictoraccchttrunggianhahckhcnh serotonin,bradikinin,histamin ngnsicmgic(ngoivi)nnccthucnhmnycxpvo nhm gim au ngoi vi [2].Thucgimaungoivibaogm:thucgimau - h st - chngvimv paracetamol. Ch nhtrongiutr au: au mc nh vva:auu,aubng kinh, au khp[4]. Tcdng khngmongmun:Lotd dy,suythn,chymumtsthuc nh aspirin gy mn cm (ph Quinck, ban da) [2].1.2.5.3. Thuc h tr iu trauThucchngngkinh(carbamazeplin,phenytoin),thucanthn(diazepam,clonazepam),thucginc(dantrolen,baclifen),corticoid,thuc chng trm cm (amitripty, imipramin,) thuc chng lon nhp cs dng tngtcdnggimautrongnhiutrnghpaumntnh,audo thn kinh [2].141.2.6. Mt s m hnh nghin cu tc dng gim au ca thuc Th nghim trn s au qun gy bi ha cht [13][22][28]:Nguyn tc: Koster v cng s s dng tc nhn gy au l acid acetic1%. Acidacetickchthchgiiphngccchttrunggiannhbradykinin,prostaglandinv cccytokin nh IL,TNFgycnaudovim.Nuthucc tc dng gim au th s lng cn au qun s gim.Phmvipdng: Th nghimgyauqunlth nghimthngdngnht kho st tc dng ca cc thuc gim au khng gy ng.u im: n gin, d p dng.Nhc im: Vic m s cn au qun ph thuc vo ngi quan st. Th nghim mm nng [13]:Nguyntc: tchutlnmyophnx bngbnnhit cnhit nnhl551 C.Dngngh bmgiyxcnhthigianphn ngaucatngcon(lkhongthi giantnht lctchutlnmynkhichutcphn nglimchnsauhocnhylncao tmcchtrnkhitmkimloinng).Nuthucth nghimctcdnggimauthchuts khngchoc chm xut hin cc phn x trn.nhgi: Xcnh thigianphn ngautrungbnhca ngthnghim. So snh kt qu gia l th v l chng.Phm vi p dng: th nghim tc dng ca thuc gim au trung ng.uim:tinhnhvquanstd dng.Sb snglcctcdnggim au trung ng ca thuc.Nhc im: Khng xc nh c mc liu ti u.1.3. Tng quan v i tng nghin cu1.4.1. Ngun gc v c im ca tectoridinTecan lmt flavonoidc cha 95% tectoridin c chitxut t thn rX can.X canhaycngilR qut,tnkhoahc BelamcandachinensisLem., h La dn - Iridaceae. X can l cy tho, sng nhiu nm, cao 0,50-1m.Thnr mcb,phnnhnhnhiu.Thnngnbaobcbinhngb l.L15hnh di, di 30 cm, rng 2 cm, gc p ln nhau, u nhn, gn song song, haimt nhn, gn nh cng mu, ton b cc l xp thnh mt phng v xe ra nhciqut.Cmhoaphnnhnh,di30-40cm,lbcdngvy;hoaccungdi, xp trn nhnh nh nhng tn n, mu vng cam im nhng m ta; dicrng nh hnhmimc;trng c cnhrngvdihnli;nh 3, dnh gc cnh hoa, bu 3 . Qu nang, hnh trng; ht nhiu, mu en bng [11].T thnr X canchitcbelamcandin(C24H24O12)vtectoridin(C22H22O11), v cc glycosid khc nh iridin (C24H28O4) v shekarin [5].Tectoridinthyphnbih vikhunngruts choglucosevtectorigenin (tinh th hnh phin, chy 227-230 C) [5].Tectoridin c trong thn r X can vi hm lng 1,5% [5].Hnh 1.2: Cu trc ha hc ca tectoridin.1.4.2. Mts nghincu v tcdng sinhhc ca tectoridinv mts dchchit t X can Cc nghin cu v tc dng chng vim:Ktqu nghincucaHongJvcngs chothytectoridin,tectorigenin chit t r ca loi Belamcanda chinensis v mt s cc cht chitxut t cc loi tho dc truyn thng khc nh plantycodin, imperatorin ctcdng cch s cm ngCOX-2,vth chngctcdng cch s tothnh prostaglandin E2(mt cht trung gian ha hc lin quan n hai qu trnhvim v au) trn i thc bo chut [19].MtnghincukhccaYongPilKimvcngs cngch rarngcch chngvimcatectoridinvtectorigeninlthngquavic cch tng15hnh di, di 30 cm, rng 2 cm, gc p ln nhau, u nhn, gn song song, haimt nhn, gn nh cng mu, ton b cc l xp thnh mt phng v xe ra nhciqut.Cmhoaphnnhnh,di30-40cm,lbcdngvy;hoaccungdi, xp trn nhnh nh nhng tn n, mu vng cam im nhng m ta; dicrng nh hnhmimc;trng c cnhrngvdihnli;nh 3, dnh gc cnh hoa, bu 3 . Qu nang, hnh trng; ht nhiu, mu en bng [11].T thnr X canchitcbelamcandin(C24H24O12)vtectoridin(C22H22O11), v cc glycosid khc nh iridin (C24H28O4) v shekarin [5].Tectoridinthyphnbih vikhunngruts choglucosevtectorigenin (tinh th hnh phin, chy 227-230 C) [5].Tectoridin c trong thn r X can vi hm lng 1,5% [5].Hnh 1.2: Cu trc ha hc ca tectoridin.1.4.2. Mts nghincu v tcdng sinhhc ca tectoridinv mts dchchit t X can Cc nghin cu v tc dng chng vim:Ktqu nghincucaHongJvcngs chothytectoridin,tectorigenin chit t r ca loi Belamcanda chinensis v mt s cc cht chitxut t cc loi tho dc truyn thng khc nh plantycodin, imperatorin ctcdng cch s cm ngCOX-2,vth chngctcdng cch s tothnh prostaglandin E2(mt cht trung gian ha hc lin quan n hai qu trnhvim v au) trn i thc bo chut [19].MtnghincukhccaYongPilKimvcngs cngch rarngcch chngvimcatectoridinvtectorigeninlthngquavic cch tng15hnh di, di 30 cm, rng 2 cm, gc p ln nhau, u nhn, gn song song, haimt nhn, gn nh cng mu, ton b cc l xp thnh mt phng v xe ra nhciqut.Cmhoaphnnhnh,di30-40cm,lbcdngvy;hoaccungdi, xp trn nhnh nh nhng tn n, mu vng cam im nhng m ta; dicrng nh hnhmimc;trng c cnhrngvdihnli;nh 3, dnh gc cnh hoa, bu 3 . Qu nang, hnh trng; ht nhiu, mu en bng [11].T thnr X canchitcbelamcandin(C24H24O12)vtectoridin(C22H22O11), v cc glycosid khc nh iridin (C24H28O4) v shekarin [5].Tectoridinthyphnbih vikhunngruts choglucosevtectorigenin (tinh th hnh phin, chy 227-230 C) [5].Tectoridin c trong thn r X can vi hm lng 1,5% [5].Hnh 1.2: Cu trc ha hc ca tectoridin.1.4.2. Mts nghincu v tcdng sinhhc ca tectoridinv mts dchchit t X can Cc nghin cu v tc dng chng vim:Ktqu nghincucaHongJvcngs chothytectoridin,tectorigenin chit t r ca loi Belamcanda chinensis v mt s cc cht chitxut t cc loi tho dc truyn thng khc nh plantycodin, imperatorin ctcdng cch s cm ngCOX-2,vth chngctcdng cch s tothnh prostaglandin E2(mt cht trung gian ha hc lin quan n hai qu trnhvim v au) trn i thc bo chut [19].MtnghincukhccaYongPilKimvcngs cngch rarngcch chngvimcatectoridinvtectorigeninlthngquavic cch tng16hpPGE2tit bovim.Nghincucngphthinc 2chtukhng cch s gii phng acid arachidonic [31]. Cc nghin cu khc:YuXiongavcngs nghincu tcdngbov gancatectoridinv cch ca n.Trongnghincunytectoridincchitxutt hoa caP. lobata (Willd.) Ohwi.Nghincuctinhnhtrnchutgycganbng ethanol (vi liu 5g/kg cn nng/12h/1 ln), tng cng ba liu. 1h sau khingvtnghincunhnliuethanol cui cng, chochutungtectoridin(25,50v 100mg/kg) nmln trongba ngy lin tip. Lymuvgitchutti thiim 4h sau khi iutr bng tectoridin lmgiiphugan. Ktquca nghin cu cho thy iu tr bng tectoridin lm gim c tnh ca ethanoltrngan,c th:Tectoridin cch tng serumglutamo-oxalotransaminase(SGOT)v serumglutamo-pyruvictransaminase (SGPT), triglycerid v cchs ri lon chc nng ty th gan. Hn na, tectoridin cng lm gim mc biuhin ca PPAR vccgen mctiu, baogmc acyl-CoAdehydrogenase chui trungbnh (MCAD), acyl-CoA oxidase (ACO) v 4Acytochrome P450 (CYP 4A) mRNA v gy gimhotngcaenzym ny.iuchngt tectoridin ctcdng bov gan,gimnhimm gandoethanol ch yu l thng qua vic gy gin on con ng iu ha PPAR vci thin chc nng ca ty lp th ti gan [32].SangHoonJungvcngs cngtinhnhnhgitcdng cchtn thng gan gy bi carbon tetrachlorid (CCl4) ca tectorigenin v tectoridinphn lp t thn r Belamcanda chinensis c in vitro v in vivo. Tectorigenin vtectoridinulmgimngk hot enzymtransaminasehuytthanhcachutnhimcCCI4.C haihpchtnycnglmgiatngmnhm ccenzymchngoxyhanhhepatic-ytosolicsuperoxidedismutase(SOD),catalasevglutathioneperoxidase(GSH-px).Nhngktqu nygirngtectorigenin v tectoridin phn lp t thn r ca B. chinensis khng ch c tc17dng chng oxy ha m cn c tc dng bo v gan chut trong trng hp bnhim c bi CCI4[26].NghincukhccaSangHoonJungvcngs v tcdngchngtomchvchngkhi uca tectoridinvtectorigeninchothyc 2chtuctcdnglmgimqutrnhtomchv cch ngk stng khilngkhi u trn chut gy u bng t bo, tng ng l 24.8% v 44.2% [27].Ngoira,trn invitro caocnthnr X canctcdng cch ccchng vi khun: Streptococcus pneumonia, Streptococcus pneumonia, Bordetellapertussis, Bacillussubtilis;vctcdngyuiviccchngvikhun:Staphylococcusaureus, Shigelladysenteriae,Sh.shigae,Enterococcus.L Xcan khng th hin tc dng c ch cc chng vi khun trn [12].Theo tc gi Tt Li, thn r X can c tc dng chng vim trong mhnhgyphbnchnbngkaolin vgy uhtthcnghimbngamian chutcngtrng,vcctnhthp.Flavonoidtonphnca X canctcdng c ch yu hot tnh ca men polypheniloxydase huyt thanh ngi. Hottnhcamennytronghuytthanhngitngrrttrongccbnhnhimkhun, trong vim cp tnh hoc mn tnh [12].18CHNG 2: I TNG V PHNG PHP NGHIN CU2.1. I TNG NGHIN CU2.1.1. ng vt nghin cuChut nht trng, chngSwiss, kho mnh, c hai ging, khi lng trungbnh18-20g( nghin cutcdnggimauvctnhcp)do VinVsinh dch t trung ng cung cp.Chutcngtrngc haiging,kho mnh, khilng180 220gnghin cu tc dng chng vim v nh gi c tnh bn trng din do Vinqun Y cung cp.ng vt th nghim sau khi mua v c nui n nh 5 ngy trc khith nghim, c n thc n chun do Vin v sinh dch t H Ni cung cp,ung nc t do.2.1.2. Dng c, ha cht nghin cu Thuc v ha cht nghin cu:- Ch phmTecan dngbtkhmuvng,hmlngtectoridin95%,chit xut t thn r X can do Ts. L Minh H, vin Ha Hc cc hp cht tnhin cung cp.- Indomethacin bt tinh khit, l 200 mg do Vin Kim Nghim B Y tcung cp.- Aspegicbtphadungdchung,hmlng100mg/gidoCngtySanofi Synthelabo cung cp.- Cchachtttiuchunphngthnghimnhether,NaCMC,carrageenin, dung dch acid acetic 1%. My mc, thit b, dng c:- T lnh, t sy, t m Memmert.- Cn phn tch Precisa XB 220A v cn k thut GM 312.- ng h bm giy.- Bm v kim tim u t.19- Dngc oth tchchnchut:Thitb Plethymometermodel7140hng Ugo basile.- Myxtnghimhuythc CELLDIFF-3,hng BIOREXFortress - AnhQuc.- My xt nghim sinh ha UNILYZER 920, hng AMS - Anh Quc.2.2. PHNG PHP NGHIN CU2.2.1. Phng php nh gi tc dng gim auTin hnh nh gi tc dng gim au theo m hnh gy au qun caKostler [13][28].Chut nht trng, c hai ging, khe mnh cn nng 18-20g. Chut cchia lm 4 l.L 1 (n=11): Ung NaCMC 0,5% vi liu 0,1 ml/10g cn nng.L 2 (n=9): Ung aspirin nng 24 mg/1ml vi liu 0,1ml/10g cn nng(tng ng vi liu 240 mg aspirin/kg).L 3 (n=10): Ung Tecan nng 10mg/1ml vi liu 0,1ml/10g cn nng,(tng ng vi liu 100 mg Tecan/kg).L 4 (n=11): Ung Tecan nng 30mg/1ml vi liu 0,1ml/10g cn nng(tng ng vi liu 300 mg Tecan/kg).Vi n l s chut mi l.Qu trnh th nghim c tin hnh theo s sau:Cho chut ung mu th, 30 pht sau khi ung mu th, gy au qunbng cch tim mng bng chut dung dch acid acetic 1% vi liu 0,1ml/10gm s cn au qun trongmi 5 pht-30 phtCho chutung mu thTim mng bng acidacetic30 phtNui chut n nh 5ngy20chut. m s cn au qun trong tng 5 pht mt n pht th 30. Biu hinca cn au qun l c bng co li v chi sau dui thng.So snh cc l ung mu th vi cc l chng.2.2.2. Phng php nh gi tc dng chng vim cpTinhnhnhgitcdngchngvimcpcaTecanngungtheophng php c m t trong cc ti liu [13][22][28].Chut cngtrngc haigingkhemnh,cnnng180-220g.Chutc chia lm 3 l:L 1 (n=8): Ung NaCMC 0,5% vi liu 1ml/1kg cn nng.L2 (n=10):Ungindomethacinnng 1mg/1mlviliu1ml/1kg cnnng, tng ng vi liu 10mg indomethacin/kg.L3(n=9):UngTecannng 6mg/1mlviliu1ml/1kgcnnng,tng ng vi liu 60mg tectoridin/kg.Chtgyvim: S dngdungdchcarrageenin1%cphatrongdungdchNaCl0,9%,cchunb trckhith nghim2gi carrageenintrng n hon ton.Qu trnh th nghim c tin hnh theo s sau:Chutcngsaukhi cnui nnhtrongiukinphngthnghim, c gy vim bn chn bng cch tim di da lng bn chn 0,05 mlcarrageenin1%.Chochutungthuc1ngyv30phttrckhigyvim.oth tchchnchut ccthiimngaytrckhigyvim(0h),saukhigyvim3hh,5h,7hv24h.Sosnhmc phchnchutcal3(ungmu th) vi l 1 v l 2 nh gi tc dng chng vim ca mu th.3h 5h 6h 7ho th tch bn chn chut0hUngmu thGy vimNui nnh 5 ngy-0,5h21Mc ph chn chut c tnh theo cng thc [13]:Vt-VoX= x100%VoTrong :X: ph tnh theo %Vo: Th tch chn chut trc khi gy vim.Vt: Th tch chn chut thi im t sau khi gy vim.2.2.3. Phng php nh gi c tnh cp tnhTinhnhnhgi,xcnhctnhcptnhcamuth theongung [24]: Nguyntctinhnh:Chutnhtcchoungtectoridinviliutng dn, theo di chut lin tc trong vng 4 gi, t l cht trong 72 gi v ccdu hiu khc trong vng 7 ngy sau khi ung tectoridin.Xc nh LD50(nu c) theo phng php Litchfield Wilconxon. Tin hnh:Nghin cu c tin hnh theo s sau: chut nhn i 4 gi trc khi cho ung mu th, cho ung nc t do.Thm d kh nng gy c ca mu th trn mt s chut bng cch chia chutthnh 3 l, mi l 3 con. Cho chut ung cc liu tectoridin nh sau:L 1: Ung Tecan 3g/kg cn nng.L 2: Ung Tecan 4g/kg cn nng.L 3: Ung Tecan 5g/kg cn nng.Cho chutnhn i0hCho chutung mu thCho chut ntr li4h72h7ngyTheo di lin tc cc biuhin ca chut2h22Chutcchontr li2gi sau khiungthuc,ncungbnhthng.Theodichutlintctrongvng4gi u,theodis chutchttrong vng 72 gi v tip tc theo di 7 ngy sau khi dng ch phm th.Ktqu thmdchothychut ttc cclkhngcconnocht,khng quan st thy bt c biu hin bt thng no xy ra chut. V vy, ccbcnhgictnhcptnhtiptheoctinhnhnhsau:Chiachutthnh 2 l, mi l 10 con:L 1: Ung dung mi pha thuc (NaCMC 0,5%).L 2: Ung Tecan vi liu 5g/kg cn nng. Cc ch tiu theo di:- Tnhtrngchungcachut:hotngt nhin,tth,musc(mi,tai, ui), lng, phn, nc tiu- T l chut cht trong vng 72 gi.- Khi c chut cht, m quan st i th cc c quan ph tng. Nu cn,lm thm vi th xc nh nguyn nhn.2.2.4. Phng php nh gi c tnh bn trng dinnhgictnhbntrngdincaTecantrnchutcngtrng,tinhnh theo hng dn ca WHO 1997 v hng dn trong ti liu [13].Chut cng trng c chia lm 3 l, mi l 9 con:L 1: Ung dung mi pha thuc NaCMC 0,5%.L 2: Ung Tecan liu 60 mg/kg cn nng/ngy (liu tng ng vi liuc tc dng dc l).L 3: Ung Tecan liu 180 mg/kg cn nng/ngy.Mu th c pha thnh dng hn dch trong NaCMC m bo th tchcho ung ng u tt c cc l (0,2 ml/kg cn nng/ngy).Nghin cu c tin hnh theo s sau:Nui n nh 5N0N14N28Theo di chut v cho chut ung mu th vo 9hhng ngyLy mu chut23Cho chut ung mu th hng ngy: 1 ln/ngy theo ng l vo khong 9 gisng.Thi gian cho ung mu th: 28 ngy (4 tun) lin tc.Cc ch tiu theo di, nh gi trc v trong qu trnh nghin cu:- Tnhtrngchung:Theodi vghichpccbiuhin nhgispht trin chung ca c th ng vt th nghim. C th, cc thng s theo digm:+Hnh vi: Tng i li, gim i li, nm im, run ry, co git+ Lng (mt, dng ng, rng) v cc c quan: Mt, mi+ Tnh trng n, ung.+ Quan st phn v nc tiu.+Cnnng:Theodicnnngchutticcthiimtrckhibtudngmuth (N0); 14ngysaukhidngmuth (N14)vsaukhichoungmu th 28 ngy (N28).- nh gi nh hng ca Tecan trn cc thng s v huyt hc: Xc nhs lng hng cu, bch cu, tiu cu, t l th tch huyt cu trong mu (HCT)v t l huyt sc t (Hb) ti cc thi im N0, N14v N28.- nhgi nhhngcaTecantichcnnggan:nhlnghotserumglutamo-oxalo transaminase (SGOT)v serumglutamo-pyruvictransaminase (SGPT), cholesterol ton phn, protein ton phn ti cc thi imN0, N14, N28.- nh gi nh hng ca Tecan ti chc nng thn: nh lng hot creatinin huyt tng ti cc thi im N0, N14v N28.- Mbnhhc:Sau28ngychochut ungmuth,git30%s chutcamil(3chut/l) quanstv ith vvith gan,thncachut cc l thc nghim.2.3. Phng php x l s liuD liu c d tr, phn tch bng phn mm SPSS 16.0 v c biudin di dng gi tr trung bnh (XSE), s dng kim nh One-way Anova24vi hu kim post-hoc so snh s khc bit gia cc l. S khc bit c ngha thng k nu p0,05).- thiimngyth14(N14)vngyth28(N28) saukhichochutung Tecan cn nng chut khng c s khc bit c ngha thng k c 3 l(p>0,05). Tuynhin lchutungTecan 180mg/kg chutkhngtngcn,thmchcxuhnggimcnmcds khcbitgiacnnngchuttithi im sau ung mu th 28 ngy v sau ung mu th 14 ngy l khng c ngha thng k (p> 0,05).293.1.4.2. Kt qu nh hng ca Tecan trn cc thng s huyt hcKtqunh lng:S lnghngcu(HC),nnghemoglobin(Hb),tlhematocrit(HCT),slngbchcu(BC),slngtiucu(PLT)ticc thi im ngay trc khi cho ung mu th (N0), sau khi cho ung mu th14ngy(N14)vsaukhiungthuc28ngy(N28)ctrnhby bng3.4(trang 31) v bng 3.5 (trang 32).nh hng ca Tecan trn cc cc ch s: HC, Hb, HCT nh sau:Bng 3.4. nh hng ca Tecan trn cc thng s huyt hc HC, Hb vHCT ca chut thc nghimMu th nHC Hb HCTN0N14N28N0N14N28N0N14N28L 1:NaCMC97,26 0,696,70 0,327,83 0,5113,22 1,2911,73 0,8212,57 0,9641,14 3,8937,37 1,8343,59 3,15L 2:Tecan 60mg/kg96,84 0,435,81 0,376,56 0,5112,79 0,5911,40 0,6111,89 0,7138,84 1,6031,95 1,24*36,79 2,01L 3:Tecan 180mg/kg96,29 0,5311,53 8,805,76 0,4411,12 1,048,91 1,3810,04 0,8235,17 3,0026,02 4,1131,14 2,35Ch thch: (*) p0,05).- Tithiimngyth 14,thngs hematocritcalth 1(ungtectoridin60mg/kgcnnng) thphnrrtsovithiimtrckhiungthuc (p0,05) (bng 3.4).nh hng ca Tecan trn s lng tiu cu v s lng bch cu nh sau:Bng 3.5. nh hng ca Tecan trn cc thng s huyt hc PLT v BCca chut thc nghimMu th nPLT BCN0N14N28N0N14N28L 1:NaCMC9573,78 56,12475,67 70,72565,44 34,4413,44 2,6517,56 2,8515,89 1,59L 2:Tecan 60mg/kg9569,22 41,26308,24 34,12*485,34 37,0814,67 1,6715,53 2,0312,36 1,35L 3: Tecan180 mg/kg9507,67 53,22314,11 45,57418,66 35,8316,89 1,1813,41 2,089,46 2,01Ch thch: (*) p0,05).- Tithiimngyth 14,s lngtiucucalth 1(ungtectoridin60mg/kgcnnng) thphnrrtsovithiimtrckhiungthuc (p0,05) (bng 3.4).31nhhngcaTecantrntlbchcu lympho(LYM),tlbchcuht nh sau:Bng 3.6. nh hng ca Tecan trn cng thc bch cu ca chut thcnghimL/ Mu thnCng thc bch cuLYM (%) Bch cu ht (%)N0N14N28N0N14N28L 1:NaCMC986,56 2,6582,44 2,8584,11 1,598,82 0,818,32 1,8310,29 1,19L 2:Tecan 60 mg/kg985,33 1,6774,53 2,0377,76 1,356,59 0,456,77 0,819,65 2,02L 3:Tecan 180 mg/kg983,11 1,1859,59 2,0865,79 2,016,84 1,144,76 1,396,49 1,36Nhn xt: Tic3thiimnghincu,khngthycskhcbitvcng thc bch cu gia cc l thc nghim (p>0.05) (bng 3.5).3.1.4.3. Kt qu nh gi nh hng ca Tecan n chc nng gan: Kt qu nh lng SGPT, SGOT, cholesterol ton phn, protein tonphn ti cc thi im nghin cu c trnh by trong bng 3.6 v bng 3.7.Bng 3.7. nh hng ca tectoridin n hot SGPT, SGOTL/ Mu thnSGPT (U/L) SGOT (U/L)N0N14N28N0N14N28L 1:NaCMC975,53 13,6380,39 12,3564,94 8,84222,37 12,64309,50 8,12229,48 20,87L 2:Tecan 60 mg/kg955,92 6,7973,38 12,0646,44 2,98196,46 15,39290,6 24,44215,34 15,69L 3:Tecan 180 mg/kg985,98 10,3883,40 23,8362,13 6,23270,19 21,60263,83 20,46244,64 17,4632Nhn xt: Ti 3 thi im nghin cu, khng thy c s khc bit v hot SGPT v SGOT cc l th nghim (p> 0,05). nh hng ca Tecan ln nng protein ton phn huyt tng vnng cholesterol ton phn c th hin trong bng 3.7.Bng 3.8. nh hng ca Tecan n nng cholesterol ton phnv protein ton phn.L/ MuthnCh s nghin cuProtein ton phn(g/dL)Cholesterol ton phn(mmol/L)N0N14N28N0N14N28L 1:NaCMC938,93 5,5435,11 1,7152,32 1,372,30 0,491,81 0,081,43 0,08L 2:Tecan 60mg/kg933,11 0,3833,20 1,2358,00 4,05*#1,73 0,091,50 0,111,56 0,05L 3:Tecan 180mg/kg932,79 1,6139,69 3,6657,56 2,51*#2,11 0,081,76 0,11*1,71 0,11Ch thch:(*) p < 0,05 khi so snh vi thi im trc khi cho ung mu th(#) p < 0,05 khi so snh vi l chng.Nhn xt:- Ti thi im ngy th 14: Khng thy s khc bit v thng s proteinton phn v cholesterol ton phn gia cc l thc nghim (p> 0,05).- Ti thi im ngy th 28: Ch s nng protein ton phn c l th1(Tecan60mg/kg) vlth2(Tecan180mg/kg)khc bitc nghasoviccchslchngvthiimtrckhiungmuth(p< 0,05).Cth:Protein ton phn c 2 l ung thuc th u tng nh tng ng l 10.8% v10%.33Nh vy: Nu s dng tectoridin ko di trn 4 tun c th lm nh hngn chc nng tng hp protein ca gan. Kt qu quan st i th gan chut sau 28 ngy ung thuc nh sau: c 2 l ung mu th v l ung t dc pha thuc gan chut c c im mtgannhn,mtbnhthng,mu,khngcxunghuyt,khngcduhiu tn thng.3.1.4.4. Kt qu nh gi nh hng ca Tecan n chc nng thn Ktqu nhlngcreatinin cclthnghimctrnhbytrongbng 3.8:Bng 3.9. nh hng ca Tecan n thng s creatinin huyt thanh cachut thc nghimL/ Mu thnCreatinin (mol/L)N0N14N28L 1:NaCMC9 68,95 5,79 71,32 3,14 59,01 2,54L 2:Tecan 60 mg/kg9 70,16 1,82 69,31 2,77 56,49 3,20L 3:Tecan 180 mg/kg9 73,59 2,49 65,33 3,37 58,42 1,42Nhn xt: Sau4tunungTecan,hmlngcreatinintrongmuchutkhng c s thay i khc bit so vi l chng (p>0,05). Ktqui thchutsau28ngyungmuth chothythnmcbnh thng, mt chc bnh thng, mu thm, mt nhn, mu , khngthy m sung huyt v m tn thng. Ktququanstcutrcviththncachutsau28ngy:Cuthnbnh thng, khng c du hiu tn thng.343.2. BN LUN3.2.1. V tc dng gim au ca Tecan nh gi tc dng gim au ca mt mu th trn thc nghim, cc thnghim thng c tin hnh trn ng vt c gy au bng nhiu phngphpkhc nhaunh:Gyaubngnhit(phngphpmmnng),gyaubngcchkpui,gyaubnghacht(bradykinin,prostaglandin,acidacetic).Tronggyauqunlphngphpthngcdng khost tc dng ca cc thuc gim au [13]. Trong nghin cu ny, chng ti chochutungTecanviccmcliu 100mg/kgv300mg/kg.Ktqu nghincucachngtichothy haimcliu 100 mg/kgv 300 mg/kgcnnngchut nht, Tecan cho hiu qu gim au tng ng nhau (p>0.05). Nh vytrong nhng nghin cu tip theo, chng ti xut mc liu ca Tecan l 100mg/kg i vi chut nht.Tectoridinlmtglycosidcchittcht dchchitthnr X can.Khib thyphn,tectoridinb mtphnglucose tr thnhdnggeninltectorigenin (Hnh 4.1) [5][19][26].Hnh 3.1: S thy phn tectoridin thnh tectorigenin di tc ng caacidHCl v vi khun Bacteriodes spercoris trong ng rut ca ngi[19][26].Bacteriodes spercoristrong ng rut ngi.35Trong mt nghin cu ca Ths. Th Nguyt Qu v cng s ch ratectorigenin th hin tc dng gim s cn au qun ba mc liu 50mg/kg,100mg/kg v 200mg/kg trong liu 100mg/kg cho hiu qu gim au tt nht[1]. Cha th kt lun tectoridin hay tectorigenin c hiu qu gim au tt hndo hai th nghim khng tin hnh song song nhng c th tc dng gim auca tectoridin c lin quan n dng chuyn ha c hot tnh ca n ltectorigenin.3.2.2. Bn lun v tc dng chng vim nghin cu tc dng chng vim, chng ti la chn m hnh gy vimbnchnchutbngcarragenin,ylmhnhth nghimtcdngchngvimcpkinhin,tinhnhngin,thuntin,thigiantinhnhnhanh.Carrageenin l cht tan trong nc to thnh dung dch, do s tim c liuchnh xc, to ph n nh [6]. Mt khc, sau khi tim carrageenin, p ngvimtintrintheo2pha,phautincctrngbngs giiphnghistamin,serotoninvcckinin,pha th haictrngbis giiphngprostaglandin, y l nhng cht trung gian gy ph bn chn chut. V vy mhnhnghin cu tcdng gimphdocarrageeninphhp nghin cu cccht c th c tc dng c ch ring l hoc ng thi cc cht trung gian hahc trn [24]. C ch trn cng ph hp vi c ch chng vim (tin hnh trnin vitro) c bo co ca tectoridin l c ch s tng hp prostaglandin E2[18][30].Ktqu nghincuch raTecanliu60mg/kgth hintcdngchngvimcp 3thiim5h,6hv7hsaukhigyvim,tcdngnytngngviindomethacin10mg/kg thiim6hv7hsaukhigyvim.ViclachnliuTecan 60 mg/kgcnnnglktqu caphptnhngoisuyt liuthucth hintcdnggimautrnchutnht(liugimau trn chut nht l 100 mg/kg cn nng, h s hiu chnh sang chut cng l7/12 [13]).TheoYongPilKimvcngs,tectoridinvtectorigeninctcdngchngvimdo cch tnghpprostaglandinE2(PGE2).Nhvyktqu36nghin cu trn in vivo ca chng ti hon ton ph hp vi kt qu ca cc tcgi trn. ng thi, nghin cu trn cng ch ra tectorigenin c hiu lc c chPGE2mnh hn tectoridin [30].MtnghincukhccaKwangSeokAhnvcngs phthinirigenin chit xut t r ca loi Belamcanda chinensis cng c tc dng chngvim trn i thc bo chut. Kt qu ca nghin cu ch ra rng Irigenin cngc ch tng hp nitric oxit v cyclooxygenase mRNAs ng thi li khng gyc t bo.Nhvyirigeninchitxutt r caX cancngctcdngchng vim [19].Theo[4]thnr X canctcdngchngvimtrongmhnhgyphbnchnchutvikaolin,vgyuhtthcnghimviamian chutcngtrng.Flavonoidtonphncax canctcdng cch yuhottnhcamenpolyphenoloxydasehuytthanhngi invitro.Hottnhcamennytronghuytthanhngitngrrttrongccbnhnhimkhun,trongcctrng thi vim cp v mn tnh, trong cc bnh bch cu, x gan v tng nngtuyt gip.3.2.3. Bn lun v c tnh ca Tecan c tnh cpCho chut nht trng ung Tecan ti liu 5g/kg chut (l liu cao nht nn thivicchotchttinhkhittheoOECD[23])khngthycs thayibtthngnotrnhotngcachut,khngcchutnochttrongvng72giv 7 ngy sau khi ung thuc th. V vy theo bng phn loi ca OECD th Tecanl cht khng c c tnh. c tnh bn trng dinTrong sut thi gian th nghim ko di 4 tun lin tc, chut cng trng c 3 l (l ung dung mi pha mu th, l ung Tecan liu 60 mg/kg cn nngv l ung Tecan liu 180 mg/kg cn nng) u khng c biu hin bt thngno mc d mc 60 mg/kg chut nghin cu khng t mc tng cn bng lchng nhng liu cao hn (180mg/kg) Tecan li khng th hin tc dng ny.37Do,chath ktlunTecancgy nhhngncnnngcangvtnghin cu khi cho ung lin tc trong 28 ngy.S lngvchtlngcct bomuphnnhtnhtrngcacquanto mu. Nu thuc tc ng n c quan to mu s lm thay i s lng vchtlngcct bomu[13].Vvy nhgictnhbntrngdincaTecantrnh tomu,chngtitinhnhnhlngs lnghngcu,hemoglobin,hematocrit,s lngtiucuvs lngbchcu.Ktqusau4tuntheodi,tibathiimnghincu,ccch s v s lnghngcu,nng hemoglobin, t l hematocritv s lngbchcuukhngcs khcbitcnghthng kgiacclth nghim.NhvyTecan liu60 mg/kgcnnngchutcngtrng(liuctcdngdcl ngvtthnghim) v liu gp 3 ln 180mg/kg cn nng khng c c tnh trn cc chcnng to mu ca chut cng trng.Khinhgi nhhngcaTecanlnchcnngthncachut, cthnhgithngquanngcreatininhuytvurhuyt.Creatininhuytlthnhphn nnhnhttrongmu,hunhkhngph thucvoch nhoc nhng thay i sinh l, m ch ph thuc vo kh nng o thi ca thn.Khicuthnb tnthng,nng creatininhuyttngsmhnurhuyt.Creatininhuytlch tiutincynnthngcdng theodiv nhgichcnngthn. Vvytrongnghincunychngtilachnthngscreatininnhgichcnngthn..Ktqu nhgi trnchutcngtrng sau2tunv4tunungTecan lin tc,nng creatinintrongmuchut khng c s thay i khc bit so vi l chng.Nh vy tectoridin liutngngviliuctcdngdclvliugp3lnukhng nhhngnnng creatinin,vynnungTecankhng nhhngnchcnnglccacuthn chutcngtrng.Ktqu nyphhpvihnh nhquan st i th v cu trc vi th ca thn. nh gi nh hng ca mu th ln chc nng gan mt c quan mnhnnhiuchcnngrtquantrngtrongcth,chngti tinhnhtheo38di, nhlnghot SGOT,SGPTvnhlngnng cholesterol,proteintonphntrongmuchut.Nuthucgytnthngt boganthhot SGOT,SGPTtrongmus tng.Mtkhcnuthuc nhthngnchc nng chuyn ha lipid, chuyn ha protein th cc thng s cholesterol vproteintonphncngs b nhhng [13].Kt qu nhgi nhhng caTecantrnchcnnggan cachutcngtrng sau4tun ungmuth chothy Tecan c 2 mc liu 60 mg/kg v 180 mg/kg u khng gy tn thngt bogan,hot SGOTvSGPTkhngcs khcbitgiacclthnghim(p>0.05).Tecancngkhng nhhngnchcnngtnghp lipidcagan,phnnhthngquanng cholesteroltonphnkhngcs khcbit c 3 l.Xemxttc ngcathuctrn chcnngtnghp protein cagan, ktqu thi im ngy th 28 ca nghin cu, ch s nng protein ton phn lth 1vlth 2caohnc nghasovilchngvsovithi imtrc khi cho ung mu th (p