一、研究背景：Cisplatin [cis-diamminedichloroplatinum (II)] (CDDP), a platinum-containing anticancer drug, is one of the most commonly used potent antineoplastic agents for the treatment of a wide range of cancers (Wanget al., 2004). The Cisplatin-induced-nephrotoxicity and ototoxicity have been very well studied in both clinical and animal researches however, liver toxicity has been rarely paid attention to. Recent studies in our laboratory and others reported that liver toxicity is also a major dose-limiting side effect in Cisplatin-based chemotherapy (Liaoet al., 2004; Honget al., 2005; Lu and Cederbawm, 2006; Pratibhaet al., 2006; Iseriet al., 2007). Though, the mechanism underlying Cisplatins side effects are not clearly understood, it was considered to be attributed by multiple factors (Honget al., 2005; Ramesh and Reeves, 2002; Nowak, 2002; Townsend and Hanigan, 2002; Xiaoet al., 2003), amongst them included the generation of Reactive Oxygen Species (ROS), which could interfere with the antioxidant defense system, resulting in oxidative damage in different tissues (Pratibhaet al., 2006; Kocet al., 2005; Mansouret al., 2006; Irazet al., 2006) and the reaction with thiols in protein and glutathione, which could cause cell dysfunction. Up until now, a large number of studies have been focused on measures of preventing Cisplatins side effects via the simultaneous supplementation of preventive agents (Aliet al., 2006a). The findings of the studies suggested the side effects of Cisplatin could be protected using drugs and micronutrients with different chemical nature (Blakleyet al., 2001; Leitao and Blakley, 2003; Fetoniet al., 2004; Kalkaniset al., 2004; Weijlet al., 2004; Kimet al., 2005).
天晴甘美主要成分为异甘草酸镁，肝脏是异甘草酸镁的特异性靶器官。临床疗上,异甘草酸镁降ALT速度快,且安全性好,未发现以往甘草酸制剂常见的水钠潴留等不良反应,通过抗炎、保护肝细胞膜及改善肝功能的药理作用，对四氯化碳、D-氨基半乳糖等引起的化学性肝损伤模型发挥显著的保护效应。但目前在异甘草酸镁对抗肿瘤药物顺铂引起的药物性肝损伤的研究很少，本实验主要探讨异甘草酸镁对顺铂诱导的药物性肝损伤的影响及线粒体作用机制。
二、研究内容：
1、顺铂肝损伤动物模型的建立。以大鼠为实验对象，模拟临床常规的给药方式，建立大鼠顺铂肝损伤模型，收集血清、肝脏标本。
2、肝功能指标检测。通过血清ALT、AST来评价是否造模成功。
3、肝脏匀浆线粒体膜电位的检测。罗丹明123染色法检测各组大鼠线粒体的损伤情况。
成果要求：
熟悉药理学实验基本操作，评价天晴甘美对顺铂诱导的肝损伤保护作用
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