摘 要
Cisplatin（帝鉑）是最有效且被普遍使用的抗癌藥物之一，但常見的腎臟毒性副作用，使得它無法更廣泛應用於癌症的治療。近年來許多研究指出發炎反應與氧化性傷害在Cisplatin腎毒性上扮演重要角色，而脂質的過氧化也已被證實與其腎毒性有關，許多性抗氧化物如維他命C因而可減輕腎小管傷害避免急性腎衰竭。綠茶多酚具有抗氧化特性，其中以EGCG為綠茶中最主要的多酚類，EGCG在小鼠實驗已證實可抑制發炎與氧化反應，但目前尚無證據顯示EGCG可減緩Cisplatin對腎造成的傷害。本研究主要以大鼠為實驗動物探討EGCG是否在Cisplatin腎毒性上扮演保護的角色。實驗將大鼠分成控制組、Cisplatin組、EGCG組與Cisplatin加EGCG等四組。Cisplatin 6 mg/kg以腹腔注射在第0天給予，EGCG 10 mg以皮下注射在實驗前4天、前2天、第0天、第2天與第4天給予。於第0、4與6 天抽血追蹤腎功能與電解質變化以評估腎毒性之傷害程度，第6天取出腎臟備製腎組織切片以了解腎絲球，腎小管及間質組織之病理變化，最後以西方墨點法評估腎組織之NF-κB與iNOS之表現及MDA含量以了解氧化壓力與發炎反應在各組間的差別。結果顯示給予腹腔注射Cisplatin之大鼠的血清尿素氮與肌酐酸明顯上升，腎小管壞死程度也顯著增加。腎組織之MDA含量，NF-κB與iNOS的表現顯著提升。而Cisplatin造成之腎損傷包括血清及腎組織異常，在給予EGCG之大鼠均有顯著改善，即EGCG的抗發炎與抗氧化壓力特性可有效降低Cisplatin之腎毒性。

Abstract
Cisplatin is one of the most effective chemotherapeutic agents used in treatment of a variety of human solid tumors. The most common adverse side effect limiting the use of Cisplatin is nephrotoxicity. Recent studies indicate that inflammatory and oxidative signaling play critical role in pathogenesis of Cisplatin related nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with lipid peroxidation and the superoxide anion and hydroxyl radical scavenger could prevent acute renal failure through both attenuation of tubular damage and enhanced regenerative response of the damaged tubular cells. It has been shown that green tea polyphenols with antioxidant properties inhibit inflammatory and oxidative responses in mice. However, the evidence indicating the protective effect of epigallocatechin gallate (EGCG), the major polyphenol found in green tea, on Cisplatin-induced nephrotoxicity is lacking. The present study is to evaluate the effect of EGCG injection on Cisplatin-induced nephrotoxicity in rats. The male rats were divided into four groups (n = 6 each); control group, Cisplatin group, EGCG group and Cisplatin + EGCG group. The control group received only intraperitoneal normal saline injection. Cisplatin (6 mg/kg) was given single dose intraperitoneally at day 0, EGCG (10 mg/time) was given subcutaneously at day 4, day 2 and day 0 before Cisplatin challenge and day 2 and day 4 after Cisplatin injection. Nephrotoxicity was evaluated by biochemical analysis of blood and histopathological observations of rat kidney. Nuclear factor-kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and malonyldialdehyde (MDA) content were also determined in rat kidney. Cisplatin injection induced an increase in serum blood urea nitrogen, creatinine and tubular necrosis, and upregulation of NF-κB and iNOS expression and MDA content in kidney. All the increases were significantly inhibited by EGCG treatment. The results suggest that EGCG may attenuate Cisplatin induced nephrotoxicity through the anti-inflammatory/oxidative effects.

目 錄

中文摘要………………………………………………………2
英文摘要………………………………………………………3
縮寫表…………………………………………………………4
研究背景………………………………………………………5
材料與方法…………………………………………………..13
結果…………………………………………………………. 20
討論…………………………………………………………..25
圖……………………………………………………………..31
附圖…………………………………………………………..45
參考資料…………………………………………………..…52

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