异烟肼（INH）是目前结核病预防和治疗中不可替代的一线药物，但其肝脏毒性严重影响了结核病的系统治疗。课题组前期研究表明，CYP2E1介导的氧化损伤是INH引起肝毒性的关键途径，而金属硫蛋白(MT)可通过调节CYP2E1表达和抗氧化发挥肝保护作用。Nrf2-ARE信号通路是近年来发现的一种抗氧化防御通路，在抵抗CYP2E1依赖的氧化性肝损伤中发挥重要作用，提示Nrf2-ARE通路对INH的肝脏毒性具有保护效应。因此，揭示MT和Nrf2-ARE通路在对抗INH肝脏毒性中的相互关系是课题的关注点。本课题将基于INH引起肝损伤的机制，在证实Nrf2-ARE通路对INH肝脏毒性具有保护作用的基础上，通过分析肝脏不同MT表达水平下INH作用后Nrf2-ARE通路中相关分子表达的差异，揭示MT与Nrf2-ARE通路在对抗INH肝脏毒性中的关系，为进一步阐明MT对INH肝脏毒性的保护机制提供实验依据。

Isoniazid (INH) is one of the first-line antitubercular drugs, however, the hepatotoxicity during antituberculosis limited its clinical use and led to treatment interruptions and nonadherence. Our previous studies indicated that CYP2E1-mediated oxidative injury was the crucial pathway in INH-induced hepatotoxicity, and metallothionein (MT) provided protections against INH-hepatotoxicity through the mechanisms of antioxidation and CYP2E1 inhibition. Nrf2-ARE signalling pathway is a novel antioxidative defensive pathway, and plays a critical role in protection against CYP2E1-dependent hepatic oxidative injury, indicating Nrf2-ARE pathway may exhibit a protective effect on INH-induced hepatotoxicity. Therefore, illumination of the relationship between MT and Nrf2-ARE pathway in protections against INH-hepatotoxcity is our focus. Based on the hepatotoxic mechanisms of INH, we firstly attempt to confirm the hepatoprotection of Nrf2-ARE pathway; and on the conditions of different MT levels, the potential relationship between MT and Nrf2-ARE pathway is elucidated by comparing the expression differences of Nrf2-ARE pathway-related molecules following INH exposure. The findings will provide the experimental evidence for the elucidation of the hepatoprotective mechanisms of MT against INH-induced hepatotoxicity.