綠茶及右旋兒茶素與水楊酸鈉在順氯氨鉑引發的腎毒性於純系小鼠的藥效評估

Effects of green tea , (+)-catechin and sodium salicylate on cisplatin induced nephrotoxicity in inbred mice

程惠聖(Cheng Hui-Sheng)

指導教授 ： 陳世銘

臺北醫學大學/藥學院/藥學研究所/碩士(2006年)

摘要

臨床上，化學治療藥物順氯氨鉑(cisplatin, CDDP)常用於治療固體癌，其引起的腎毒性，常是限制臨床使用的主要因素。本研究利用低劑量CDDP連續投予小鼠，引發腎炎模型，以綠茶及(+)-catechin和sodium salicylate作為預防藥物，評估在此腎炎之預防效果。 實驗以6週齡雌鼠(BALB/c mice)藉由事先投予綠茶濃縮劑(GT 75, 150, 300 mg/kg/d)及其純成分(+)-catechin（CAT 25, 50, 100 mg/kg/d）、化學藥品sodium salicylate 100 mg/kg/d（S）、併用CAT 50mg + S（S + C）來評估藥物對CDDP引起腎毒性的預防效果。實驗以N-acetyl-?-D-glucosaminidase (NAG)、urinary creatinine (Ucr.)與BUN評估腎功能；腎組織以PAS染色觀察病理組織及免疫螢光染色辨別其損傷部位之特異性抗原。 實驗結果顯示，GT 150 mg/kg/d、(+)-catechin 50 mg/kg/d及S + C皆可改善腎功能，組織學上腎小管受損的情形相較於對照組也較輕微。綜合實驗結果顯示，S + C對於預防CDDP所引起的腎毒性效果最好。

關鍵字

Cisplatin腎毒性 ； 綠茶濃縮劑 ； 甲型腫瘍壞死因子 ； p21 ； 週期蛋白D1

並列摘要

Cisplatin(CDDP) is one of the most commonly used antineoplastic agent for the treatment of solid tumor. The CDDP induced nephrotoxicity is dose-related and cumulative. It is the major dose-limiting toxicity of cisplatin. We used an established CDDP induced nephrotoxicity in inbred mice model to evaluate the effect of green tea extract, (+)-catechin and sodium salicylate. Before administration of CDDP(i.p. 5mg/kg/d on day 1 to day 5), BALB/c mice（6 week, female）were administered orally with green tea extract(GT 75, 150, 300 mg/kg/d), (+)-catechin(CAT 25, 50, 100 mg/kg/d) , sodium salicylate 100 mg/kg/d(S) and combination of CAT 50 mg/kg/d and S(S + C) once daily for 10 days(on day -5 to day 5). Urinary N-acetyl-β-D-glucosaminidase(NAG), urinary creatinine (Ucr.)and BUN were determined. Renal tissues were served to histological examination (PAS stain and immunofluorescence staining). The antibodies including TNF-?, p21, cyclin D1 was chosen to recognize the specific antigens, which deposited in injury sites. The result showed that GT 150 mg/kg/d、(+)-catechin 50 mg/kg/d and S + C can ameliorate renal damage. According to the study, the effect of S + C was superior to the other groups.

並列關鍵字

Cisplatin nephrotoxicity ； tea ； p21 ； cyclin D1 ； TNF

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