人參及人參皂苷在順氯氨鉑引發的腎毒性於純系小鼠的藥效評估

Effects of ginseng and ginsenosides on cisplatin-induced nephrotoxicity in inbred mice

邱芷瑩(Chih-Yin Chiu)

指導教授 ： 陳世銘

臺北醫學大學/藥學院/藥學研究所/碩士(2007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於CDDP所引起的腎炎之預防效果。
實驗動物為6週齡母鼠（BALB/c mice），經腹腔連續五天給予5 mg/kg 的CDDP以引發腎炎。在給予CDDP前五天開始經口投予小鼠人參濃縮劑（ginseng extract，GE）125, 250, 500 mg/kg/d或人參皂苷（ginsenoside，GS）Rb1、Rd、Rg1 5 mg/kg/d做為預防藥物。實驗結果顯示，給予GE及GS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明顯減緩的趨勢。在免疫螢光染色方面，TNF-α的量明顯受到抑制，p21及PCNA的表現亦有不同程度的增加。
因此可以推論，經口投予人參濃縮劑及人參皂苷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 effect of ginseng extract (GE) and its active component, ginsenoside (GS), on cisplatin-induced nephrotoxicity.
Six-week-old female BALB/c mice were administered with 5 mg/kg of CDDP intraperitoneally once daily for 5 days. 125, 250, 500 mg/kg of GE or 5 mg/kg of GS Rb1, Rd, Rg1 were given orally once a day from 5 days before CDDP administration. GE and GS decreased urine N-acetyl-β-D-glucosaminidase (NAG), urine protein, blood urea nitrogen (BUN) and increased urine creatinine excretion at different level. All of the treatment groups ameliorated CDDP-induced renal morphological damage and diminished TNF-α deposited in injury tissue, while GE and GS Rg1 increased the expression of p21 and PCNA in renal cell.
Our findings demonstrated that GE and GS attenuate CDDP-induced nephrotixicity by inhibiting TNF-α expression and inducing cell cycle arrest to repair DNA damage. The effects of GE 250 mg/kg and GS Rg1 are the best among the concomitance groups.

並列關鍵字

Cisplatin nephrotoxicity ； ginseng ； ginsenosides ； TNF-α ； p21 ； PCNA

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