异烟肼（INH）是目前抗结核治疗的不可替代的首选药物，但其明显的肝毒性严重限制了它的临床应用，如何防治其肝损伤已成为抗结核化疗亟待解决的问题。槲皮素是具有临床应用前景的抗氧化剂。课题组前期研究表明，槲皮素对INH所致肝损伤具有保护效应，但其作用靶位与机制不清。本课题应用体内、体外试验相结合，从亚细胞器水平揭示槲皮素的作用靶标，以ROS介导的线粒体氧化损伤与MAPK信号途径为切入点，确证槲皮素对INH肝毒性的保护作用，阐明槲皮素对INH肝毒性的保护效应机制。重点探讨ROS介导的线粒体氧化损伤与MAPK信号途径在槲皮素抗INH肝毒性中的作用，以及两者之间可能的相互关系。为进一步阐明槲皮素发挥肝脏保护效应的分子机制及寻找可用于防治INH肝损伤的有效药物提供重要的理论基础和实验依据。

Isoniazid (INH) is clinically common, irreplaceable a line TB drugs, its obvious hepatotoxicity severely restricting its clinical application, how to prevent and control the hepatotoxicity has become anti-tuberculosis chemotherapy problems to be solved, and Quercetin is the antioxidants have clinical application prospects. Our previous studies show that Quercetin has a protective effect in INH-induced hepatotoxicity, but the targets and mechanisms are unclear. In the present study, this topic application in vitro or in vivo combined, on the subcellular level, to identify the targets and protect effects of quercetin. With ROS mediated mitochondrial damage and MAPK signaling pathways as the breakthrough point, this study was designed to discuss the protect effects and molecular mechanisms of quercetin on INH-induced hepatotoxicity. We will clarify the role of ROS-mediated mitochondrial damage and MAPK signal pathway in quercetin against INH-induced hepatotoxicity. The results will represent further strong experimental and theoretical evidences for the clinical application of quercetin in the prevention of INH-induced hepatotoxicity.