人參及人參皂苷 ;Rg1與 N-乙醯半胱胺酸在順氯氨鉑引發的腎毒性於純系小鼠的藥效評估

順氯氨鉑（ cisplatin ， CDDP ）是臨床上治療固體癌的常用化學治療藥物，其所引起的腎毒性常是限制臨床使用的主要原因。本研究的目的即在於評估人參及其純成分人參皂苷與 N- 乙醯半胱胺酸（ N-acetylcysteine ）作為預防藥物於 CDDP 所引起的腎炎之預防效果。實驗以 6 週齡雌鼠 (BALB/c mice, female) ，經腹腔連續五天給予 CDDP 5 mg/kg/d 以引發 CDDP 腎炎。在給予 CDDP 前五天開始經口單獨投予小鼠人參濃縮劑 (ginseng extract ， GE) 250 mg/kg/d 或人參皂苷 (ginsengoside ， GS) Rg1 5 mg/kg/d 及並分別合併 N-acetylcysteine 450 mg/kg/d 作為預防藥物。實驗結果顯示，給予 GE 、 GS Rg1 及 N-acetylcysteine 對於 N-acetyl-beta-D-glucosaminidase (NAG) 、尿中肌酸酐（ urine creatinine ）、尿蛋白（ urine protein ）與血中尿素氮（ BUN ）皆有不同程度的改善效果；腎組織損傷相較於對照組也有減緩的趨勢。在免疫螢光染色方面， TNF-alpha(tumor necrosis factor-alpha) 的量明顯受到抑制， p21 及 PCNA （ proliferating cell nuclear antigen ）的表現亦有不同程度的增加。綜合實驗結果，合併治療組對於預防 CDDP 所引起的腎毒性效果最佳。因此可以推論，經口投予人參濃縮劑、人參皂苷 Rg1 、 N-acetylcysteine 可以藉由抑制發炎反應、阻止細胞週期的前進並促進 DNA 修復以達到腎臟保護的效果。

Effects of ginseng , ginsenoside Rg1 and N-acetylcysteine on cisplatin-induced nephrotoxicity in inbred mice

Cisplatin (CDDP) is one of the most commonly used antineoplastic agents for the solid tumor treatment. The major side effect of CDDP is nephrotoxicity. It is dose-related and has become a chief limitation of its clinical use. The purpose of this study was to evaluate the preventive effects of ginseng extract (GE), its active component, ginsenoside Rg1(GS Rg1) and N-acetylcysteine (NAC) on CDDP-induced nephrotoxicity in bred mice. Six-week-old female BALB/c mice were administered with 5 mg/kg of CDDP intraperitoneally once daily for 5 days. 250 mg/kg of GE or 5 mg/kg of GS Rg1 combination with 450 mg/kg/d of NAC were given orally once a day from 5 days before CDDP administration. Urinary N-acetyl-??-D-glucosaminidase (NAG), urinary creatinine(Ucr) and blood urea nitrogen (BUN) were determined, Renal tissues were served to histological examination. The antibodies including tumor necrosis factor-alpha(TNF-alpha), p21 and proliferating cell nuclear antigen (PCNA) was chosen to recognize the specific antigens that deposited in injury sites. Our findings demonstrated that GE, GS Rg1 and NAC attenuate CDDP-induced nephrotixicity by inhibiting TNF-alpha expression and inducing cell cycle arrest to repair DNA damage.According to this study, the effect of combination treatment was superior to other group.