Tieu Luan Dlieu 2

7/27/2019 Tieu Luan Dlieu 2

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TRNG I HC Y DC HU

KHOA DC

----- 0----

TIU LUN

ti:

TM HIU VTHNG

(Taxus wallichiana Zucc)

Ging vin hng dn Sinh vin thc hin

PGS.TS Nguyn Vit Thn Chu Th H My

Lp D3A

Hu, thng 4/2013


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T VN

Cy thng c bit n t rt lu trong dn gian nh mt loi dc liuqu. Trong y hc c truyn n , l v vthng c dng tr hen, vim ph qun,tiu ho..., cnh v v dng tr bnh thc tch, giun a, nc sc ca thn non dng tr

bnh au uTrong y hc dn gian Trung Quc, thng c tc dng tiu ch, thngtim mch, gim au. ThNh K, thng dng tr bnh tim v gcy thng c dng tr bnh tiu ng.

Nm 1967, Monroe E. Wall Mansukh C. Wani phn lp t thng (TaxusBrefolia) cht paclitaxel. Vin Ung th Quc gia M pht hin hot cht ny c tnh nngcn trvic phn hy bnh thng ca vi ng, n nh vi ng, t c ch phn bo.Cng ty Bristol Myers Squibb dng hot cht trn ch ra thuc c tn thng mi ltaxol. Nm 1992, FDA chnh thc ph duyt dng taxol iu trung th bung trng, v,

phi v ung th c tcung. Trong 10 nm, BMS thu v khong 11 t USD t taxol.

Cht docetaxel chit t thng (Taxus wallichiana) tng tpaclitaxel, t chn. Cng ty Sanofi -Aventis Php ch ra thuc trcc ung th trn vi tn thng mitaxotere. Taxotere c hiu lc vi c ung th v di cn, khng p ng vi ha tranthracyclin, cn c chu u dng trong iu trung th tuyn tin lit. Doanh s trndi 2 tUSD/nm.

Mi y, cng tthng , cc nh khoa hc ch ra phm sinh hc th h minh herceptin cho ung th v, cimavax-egf cho ung th phi, song cn hn chv cha

ph bin. Gi thuc, gi xt nghim kh cao, kh ph hp vi sng ngi bnh. Dovy vi cc ung th trn, n thi im ny, ha tr bng taxol, taxotere vn gi v tr

ch lc. Ti Vit Nam, Bnh vin Ung bu TP.HCM, nm 2006 chi 19 tng muacc bit dc ny.

Hin nay, taxol, taxotere ht hn bo h c quyn. Vic sn xut hai thucgeneric tthng ang l nhu cu c t ra i vi nhiu nc, trong c nc ta.

Trin vng thng nc ta l v cng to ln. Thng Vit Nam l Taxuswallichiana Taxaceae, cng loi v c hm lng hot cht cao nh thng Php mSanofi Aventis dng sn xut taxotere. Hin thng c phn bcc vng nh TP. Lt (Lm ng) trn cao 1.700m nhng rt tha tht.

Theo nhn nh ca TS. Dng Tn Nht, Phn vin ph Phn vin Sinhhc Lt th gi tr ca cy thng ch c khuy ng ln ngay thi im tm thy chngti Vit Nam, nhng cng ch mc cnh bo v nguy c tuyt chng, t vn bo tnch cha ni n pht trin .Cch nay khong 5 nm, theo thng k ca ngnh lmnghip, qun th thng trng thnh (hng nghn nm tui) Lm ng cn khong300 cy. Nhng hin nay, vi nhng g din ra lin quan n qun th thng cuicng ny, con s c th cn li cha n vi chc cy.Mun sn xut thuc generic taxol,


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taxorete cnlng nguyn liu lncy thng .Theo tnh ton,t 1250 kg v thn chit xut ra 28 kg cao ton phn v 10 g Taxol tinh khit.

y l mt bi ton nan gii khng ch vi cc ngnh chc nng m cn i vicc nh khoa hc phi tm ra phng php,quy trnh cng ngh bo tn,pht trin

ngun gen qu gi ny.

1. TNG QUAN

1.1. C IM THC VT

1.1.1 M t thc vt

Tn khoa hc: Taxus wallichiana Zucc.

Tn Vit Nam: Thng l di, sam ht l di.

Gii (regnum) : Plantae

Ngnh (divisio) : Pinophyta

Lp (class) : Pinopsida

B (ordo) : Pinales

H (familia) : TaxaceaeChi (branch) : Taxus

MT S HNH NH CY THNG (TAXUSWALLICHIANA ZUCC.)

Hnh 2: Gthng Hinh 1: L thng Hnh 3: Thn thng


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Cy thn g trung bnh, l xanh, cao n 20m. Thn c v mu hng xm, phnnhiu mnh, khi non mu lc. L mc so le, thng xp hai dy nh mt l kp, hnh dirt hp, dng cong, di 2.53.5 cm, rng 2 3 mm, gc thun, u nhn, mt trn lmnh long thuyn, mt di c hai dy l kh. Cm hoa n tnh, khc gc, nn c vnn ci mc k l. Qu hnh trng, v cng, c ht, bao bc bi o mu hu.

S phn loi chi Taxus rt kh khn v vn cn nhiu tranh ci v nhng cythucchi Taxus rt ging nhau. Di y l bng phn loi ca Krussmann (ngic) ckh nhiu ngi chp nhn.

Bng 1: Phn loi chi Taxus

Tn thng thng Tn phn loi theo Krussmann

European yew hay English yew

Himalayan yew

Chinese yew

Japanese yew

Pacific yew

Mexiean yew

Florida yew

Canadian yew

Taxus baccata L.

T. wallichiana Zucc.

T. celebica (Warburg) Li

T. cuspidata Sieb. et Zucc.

T. brevifolia Nutt.

T.globosa Schlechtd.

T.floridana Nutt.

T. canadensis Marsh.

T.x media Rehd.

T.x hunnewelliana Rehd.

Ngoi ra, nhm Chinese yew cn c Taxus chinensis Rehd., Taxus yunnanesisCheng et L. K. Fu, Taxus mairei (Lemee and Lev.) Hu ex Liu.

Hnh 4: Quv l thng Hnh 5: Quv l thng


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1.1.2. Phn b, sinh thi

Chi Taxus c 7-8 loi trn th gii, phn b ri rc vng n i m, vng cnnhit i v nhit i ni cao bc bn cu. Vit Nam chi Taxus c 2 loi l Taxuschinensisthng gi l thng l ngn v Taxus wallichiana Zucc. gi l thng

l di.Thng l ngn: phn bTrung Quc, n , Malaysia v Vit Nam. Vit

Nam, cy phn b ri rc vng ni thuc tnh Lo Cai (Hong Lin Sn), H Ty (BaV), Ngh An (QuChu), Ha Bnh (Mai Chu), cao: 9001600m.

Thng l di: phn bNepan (vng ni Himalaya), pha bc Myanmar, ng Nam Trung Quc, n , Indonesia, Philippin v Vit Nam. Vit Nam, loi nycng ch thy mt s vng ni cao thuc tnh Khnh Ha, Lm ng ( Lt, nDng), H Giang (Thi An Qun B), cao phn b t 14001600m hoc hn.

Nhn chung, chai loi thng u thuc cy g ctrung bnh, mc rt ri rctrong kiu rng kn thng xanh m trn nh ni vi hay granit. Chng c coi lcy kha t chu bng hoc a sng, thng mc di tn mt s cy g thuc cc hLong no (Lauraceae), Mc lan (Magnoliaceae), Hi (Illiaceae)

Thng thng ra l non vo ma Xun H, nn c xut hin sm hn nnci t cui ma ng, nhng n gia ma xun nm sau cnn c v nn ci mi n.Thng sinh trng chm, ti sinh t nhin t ht kh. Tuy vy, nu trn nh ni cvi cy to, vn c th thy nhng cy con mc t ht. Vi nm gn y, mt sc snghin cu H Ni v Lt th nghim thnh cng vic nhn ging thng bngcnh.

1.3. THNH PHN HA HC

1.3.1. Thnh phn ha hc c trong l

Nm 1997, Nguyn Hu Ton Phan v cng s cng btch c haihp chtl 10-deacetylbaccatin III (1) v 19-hydroxybaccatin III (2)t l thng (Taxuswallichiana Zucc.) thu hi ti tnh Lm ng, Vit Nam.[1]


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Nm 2007, cng t l thng (Taxus wallichiana Zucc.) thu hi ti tnhLm

ng, Nguyn ThThanh Tm c lp c by hp cht:10-deacetylbaccatin III (1),19-hydroxybaccatin III (2), taxinine B (3), taxuspine F(4), 10-deacetyltaxuspine F (5), p-zydroxybenzaldehid(6),7-(-xylosyl)-10-deacetyltaxol [1]

1.3.2. Thnh phn ha hc c trong thn v r


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Nm 1995, Sunil K. Chattopadhyay v cng s c lp c 3 hp cht l:

2-acetoxy-brevifoliol (7), 2-deacetoxy-5-decinnamoyltaxinine J (8) v2-deacetoxytaxinine J (9). Ba hp cht ny cng c tch ra tl nm 1999.[1]

Nm 1981, Miller R. W. v cc cng s c lp c 1-hydroxybaccatin I(10);taxol (12)t thn cnh v r ca Taxus wallichiana.[1]


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Taxol (pacli taxel) , mtalkaloid di terpenoidthin nhin tv cy(12)[7]

1.2. C TNH V TNH CHT DC L

1.2.1. c tnh

Cao nc l thng , cho chut cng trng ci ung liu 100 v 500 mg/kg,trongnhng ngy 1-7 sau khi giao hp c tc dng c ch s ththai 60% v 80% tng ng.

V cy, l v ht thng c tc dng c nh: nn, tiu chy, m sng, c tcdng c ch tim lm gim lc co c tim, gim nhp tim v phong bnh tht do tc dngc ch knh natri v canxi.

1.2.2. Tc dng dc l theo kinh nghim dn gian

Thng l ngun dc liu rt qu trong y hc. T lu, trong y hc c truyn n, cao l kh v cao v thng c dng tr hen, vim ph qun, nc, tiu ho...;cnh v v dng tr bnh thc tch, giun a; nc sc ca thn non dng tr bnh auu...

Trong y hc dn gian Trung Quc, thng c coi l c tc dng tiu ch,thng tim mch, gim au. ThNh K, nhn dn dng tr bnh tim. c bit gcy thng c dng tr bnh tiu ng.

2. HIN TRNG:Cch nay khong 5 nm, theo thng k ca ngnh lm nghip, qun ththng

trng thnh (hng nghn nm tui) Lm ng cn khong 300 cy. Nhng hin nay,vi nhng g din ra lin quan n qun ththng cui cng ny, con s c th cnli ch rt t.

ang b tn ph nghim trng.


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Theo ng Ha Vnh Tng - Gim c Trung tm Nghin cu lm sinh Lm ng(thuc Vin Khoa hc lm nghip Vit Nam) khng nh: "Qun th thng Taxuswallichiana Zucc ni Voi c ng knh ln nht v slng nhiu nht VN. Chng tac nhiu loi thng , nhng loi Taxus wallichiana Zucc ch c duy nht Lm ngv c gi tr rt ln trong y hc". ng L Xun Tng - Trng phng Nghin cu khoa

hc (Trung tm Nghin cu lm sinh Lm ng), ngi c cng trnh khoa hc nghincu v loi thng ny trong nhiu nm, cho rng: "Thng ny sinh trng rt chm(ng knh 30cm phi mt 150 nm); cy rt qu, cht taxol chit xut t loi cy nyc th cha c mt s bnh. y l loi cy n tnh khc gc, c cy c cy ciring, nu b cht mt trong hai th khnng ti sinh rt t. Nhng cy cngn nm tuinh th ny m b cht h th qu l kinh hong".

Do m tn: Tin n ngi cht c chn trong quan ti lm bng thng s rtlinh thing, ph hcho gia nh,..., khin bn lm tc v ngi dn a phng ln voqun ththng qu him nht ca Vit Nam ca x cy qu.

Cc c quan chc nng khng quan tm

D tt c nhng l l, lp lun u rt cht ch v thuyt phc thy s cn thitv vic hnh thnh vng nguyn liu thng ti Vit Nam, nhng cho n nay vn ny vn khng thu ht c s quan tm ca nh nc cng nh cc b ch qun c linquan n loi cy ny.

Theo TS Dng Tn Nht, Phn vin ph Phn vin Sinh hc Lt, nhng gitr ca cy thng chc khuy ng ln ngay thi im ngi ta tm ra n ti Vit

Nam, nhng cng chmc cnh bo vnguy c dit vong ca loi cy ny v t vn lm sao bo tn chkhng ni n vn pht trin, khng xem y l mt vn xhi.

Sau , thng gn nh b lng qun. Nhng d n vcy thng phn lnc cc nh khoa hc tm huyt thc hin bng nhng ngun kinh ph chp v hoc ku


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gi ti trvi ngun kinh ph h trrt t i t cc t chc khoa hc, cha c bt c mtchng trnh no ly ngun kinh ph tngn sch nh nc.

3. GII PHP:

TS Dng Tn Nht cho bit: Cho n nay, Phn vin Sinh hc Lt nghin cuthnh cng nhiu chng trnh lin quan n cy thng nh: nhn ging hu tnh, vtnh; nui cy tbo thng Cc nh khoa hc tm huyt nghin cu thnh cngnhiu vn hu ch nhn rng v pht trin cy thng .

Bng phng php cy m, cc nh khoa hc ca Vin cng ngh sinh hc v thcphm, H Cng nghip TP HCM va nhn ging thnh cng cy thng .

Nhm to ra c cy con c r. Tin s m Sao Mai cho bit, t l nhn ging tnhin ca cy thng rt thp, ch khong 0,1% v cy c tri nhng khng c ht.

Vin Cng ngh sinh hc thc phm l ni u tin trong cnc to ra ccy thng con c r. Slng cy thng Vit Nam hin nay cn rt t, y l mttrong nhng ging cy qu him cn c bo tn.

Tin s Mai cho bit thm, Vin hp tc vi mt sni pht trin cy thng ny.

Nhiu ti nghin cu thng c trin khai in hnh nh:

ti:

Bi ThTng Thu, Trn Vn Minh

PTNT pha Nam v CNTBTV, Vin Sinh hc Nhit i- Hi ngh KHOA HC VCNG NGH2007

NGHIN CU NUI CY PHT SINH V TI SINH

PHIsomaTHNG (Taxus wallichiana Zucc) in vitro.

Cy thng dng Taxus sp. varwallichiana (Zucc.) Hook l loi cy b n a caVit Nam, cn st li khng qu 16 cy ti Cao nguyn lm vin Liang Biang, c ngknh thn trn 75cm, l loi cy sinh trng chm. Bo tn v pht trin cy thng Lt l mt yu cu cp thit i vi loi cy qu him c gi tr chit xut taxol phng

chng bnh ung th. Phng thc nhn ging truyn thng hin nay l gieo ht hocgim cnh hoc ghp cnh (Ho, 1998). Tuy nhin, ht mau mt sc ny mm v slnght cho mt ma tri rt thp; hn na cy gim cnh thng c hin tng sinh trngchm v ng nghing (plagiotropically) v khng thng ng (Chang etal, 2001). Nuicy vi nhn ging cy thng dng Taxus media v Taxus mairei c ghi nhntrong nhng nm gn y (Cerdeira, 1994; Chang etal, 1998), tuy nhin cy con in vitrosinh trng chm v bo lu cc b tnh ng nghing. Nui cy phi soma l mt k


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thut nui cy in vitro vt qua khnng ny mm km ca ht ging v hn ch vnsinh trng chm cy con in vitro nht l i vi cy thn g l kim (Gupta & Durzan,1987). Kt hp k thut nui cy pht sinh, ti sinh phi soma v dng ha in vitro s hnchmc thp nht tnh bo lu ng nghing cc b bng k thut vi nhn ging nngcao hiu sut nhn nhanh cy thng invitro (Amos & McCown, 1981; Chee, 1995)

Vt liu

Vt liu c a vo nui cy pht sinh tbo soma l thn v l cy thng c dng ha in vitro. T bo soma thu nhn c qua nui cy t thn c avo nghin cu nui cy tng sinh trn mi trng agar v lng. Dch huyn ph thunhn c sau 6 tun nui cy c xc nh mt v c s dng trong nui cy phtsinh v ti sinh phi soma. Mc tiu ca th nghim l tm mi trng thch hp cho nuicy pht sinh t bo soma v khnng tng sinh khi.

Kt qu

Mi trng nui cy c bn c b sung TDZ thch hp cho nui cy tng sinh tbo soma trn mi trng agar v mi trng lng; t hp cht iu h a sinh trngTDZ+ABA bsung vo mi trng nui cy thch hp cho pht sinh v ti sinh phisoma.[5]

Theo TS Nht, cho n nay, chng ta hon ton c th lm ch v vic nhn gingbng phng php v tnh gim hom. Vic trng trt, nghin cu iu kin sinh thi chocy pht trin cng c Trung tm Nghin cu lm sinh Lm ng thc hin vi 3ha

thng c trng tri thc nghim Mang Linh. y l mt iu kin rt tt VitNam c th hnh thnh v pht trin thng thnh vng nguyn liu qu gi.[4]

4.KT LUN:

Thng l mt ngun nguyn liu v cng qu gi v kh nng ti sinh hp nn

chng ta cn phi c nhng bin php bo tn ngun gen ny 1 cch hp l, cn tin hnh

a dng cc bin php nui cy t bo n, nhn ging bng phng php v tnh

thu c nhng sn phm th cp c gi tr kinh t cao p ng nhu cu cuc sng cng

nhvic s dng Taxol iu tr ung th(t thng ).

Thi gian gn y x Hip Thnh (c Trng) v vng ln cn bng rm ran

nhng li n: cc tc phm ngh thut c iu khc bng g thng s mang li

nhiu may mn cho ngi s hu,c bit ngi cht c chn trong quan ti lm bng


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thng s rt linh thing ph h cho gia nh, dng h kho mnh, pht ti pht lc,

trnh c tai ng,cc tin n tht thit ny khin bn lm tc v ngi dn a

phng ln vo qun th thng qu him nht ca Vit Nam thuc khu vc ni Voi

(Hip Thnh) him tr ca x cy qu. Do cc cquan c chc nng cn c binphp bo v cht ch ngun g qu ny.

Gi tr ca cy thng l khng th bn ci nhng thng ang ng trc

nguy c tuyt chng rt cao, vy nn mi ngi trong chng ta phi c thc bo v

ngun gen qu cng nh pht trin n nhiu ln. Do vy cn c sng thun, h trv

chung tay gp sc ca nhiu ngi cng nh cc ngnh chc nng c lin quan n vic

bo tn cng nh pht trin quy m ln vi loi cy ny.

i vi chnh quyn a phng:

- Tuyn truyn cho ngi dn hiu c ht gi tr to ln ca loi cy qu him ny.- Khuyn khch inh canh nh c, hn ch vic nh canh nh c trnh vic t

rng lm nng ry.- Giao t, ging cy vcho ngi dn pht trin ni mnh ang sinh sng.- C chnh sch u tin trong vic thu mua li cy thng cho ngi dn khi thu

hoch cng nh u tin i vi ngi trng n.i vi cc cquan chc nng nh nc:

- Trin khai vic nhn ging cy thng bng cch chit, dm cnh hoc nui cym.

- Lp ra t chc bo v, bo tn v nhn ging cy thng .- Kin nghln c quan cp trn a thng vo loi c bo tn vi nguy c cao

nht.- Mun sn xut thuc generic taxol, taxorete cn lng nguyn liu ln v nh my

chit xut quy m khng nh. D c li thi sau, trnh c vp vp m mm, thcng phi c mt d n tm ccp nh nc vi kinh ph ln c nhiu b, ngnh thamgia. Khng nh vy th d c tm huyt n my cng khng th lm c. Gii biton kh ny phi chquyt sch ca cc nh qun l.

i vi ngi dn a phng:


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- C thc bo v ti nguyn quc gia, khng nn cht ph ba bi cy thng cng nh n h khi cha c php ca a phng.

- Nhn ging cy thng v trng a phng ni mnh sinh sngTI LIU THAM KHO

[1]TRN TH THU HIN. Nghin cu thnh phn ha hc ca rcy thng (Taxuswallichiana Zucc.) h Thanh tng (Taxaceae).TP.HCM. : i hc Khoa hc T nhin,2012.

[2]http://en.wikipedia.org/wiki/Taxus_wallichiana

[3]Tp ch pht trin khoa hc v cng ngh, tp 9, s 5-2006

[4]http://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspx

[5]Bi ThTng Thu, Trn Vn Minh

PTNT pha Nam v CNTBTV, Vin Sinh hc Nhit i- Hi ngh KHOA HC VCNG NGH2007

[6]http://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htm

[7]http://en.wikipedia.org/wiki/Paclitaxel
http://en.wikipedia.org/wiki/Taxus_wallichianahttp://en.wikipedia.org/wiki/Taxus_wallichianahttp://en.wikipedia.org/wiki/Taxus_wallichianahttp://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspxhttp://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspxhttp://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspxhttp://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspxhttp://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htmhttp://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htmhttp://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htmhttp://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htmhttp://en.wikipedia.org/wiki/Paclitaxelhttp://en.wikipedia.org/wiki/Paclitaxelhttp://en.wikipedia.org/wiki/Paclitaxelhttp://en.wikipedia.org/wiki/Paclitaxelhttp://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htmhttp://suckhoedoisong.vn/2011072510038589p-1c19/bien-thong-do-thanh-than-duoc-kho-hay-de.htmhttp://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspxhttp://www.khoahoc.com.vn/khampha/sinh-vat-hoc/sinh-hoc/24130_Nhan-giong-thanh-cong-loai-thong-chua-chat-tri-ung-thu.aspxhttp://en.wikipedia.org/wiki/Taxus_wallichiana


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