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

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

黃致云(Zhi-Yun Huang)

指導教授 ： 陳世銘

臺北醫學大學/藥學院/藥學研究所/碩士(2008年)

摘要

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。

關鍵字

Cisplatin腎毒性 ； 人參 ； 人參皂苷N-乙醯半胱胺酸 ； 甲型腫瘍壞死因子 ； p21 ； 增殖細胞核抗原

並列摘要

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.

並列關鍵字

Cisplatin nephrotoxicity ； ginseng ； ginsenosides ； N-acetylcysteine ； TNF-alpha ； p21 ； PCNA

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