ADAM9是解整合素-金属蛋白酶家族的重要成员，与多种肝病的发生发展密切相关。化学性肝损伤是多种肝病的重要诱因，迄今ADAM9在化学性肝损伤中的作用及机制仍知之甚少。我们的预实验结果表明：ADAM9在四氯化碳诱导的小鼠化学性肝损伤过程中对肝脏起到重要的保护作用，ADAM9可能通过调节IL-6跨信号途径促进肝脏的修复和再生，但其作用机制有待进一步探讨。为此，体内实验我们利用ADAM9基因敲除小鼠、重组ADAM9分子、IL-6跨信号途径激活剂和抑制剂，体外实验利用转基因和RNAi技术上调或下调鼠肝星形细胞中ADAM9的表达，采用免疫组化、蛋白印迹、实时定量RT-PCR和免疫沉淀等方法，从分子、细胞、组织以及动物整体水平等多方面探讨ADAM9调控IL-6跨信号途径在四氯化碳诱导的化学性肝损伤中的重要作用及机制，能够进一步阐明化学性肝损伤后肝脏修复再生的机制，为治疗相关肝脏疾病提供新的思路和方法。

ADAM9, an important member of a disintegrin and metalloprotease (ADAM) family, is closely related with the development and progression of various liver diseases. Chemical liver injury is an important inducement for many kinds of liver diseases. At present the role and mechanism of ADAM9 in chemical liver injury are still poorly understood. The results of our preliminary experiments showed that ADAM9 play an important hepatic protective role in mice with chemical liver injury induced by carbon tetrachloride. ADAM9 may promote the repair and regeneration of the liver by regulating the IL-6 trans-signaling. But the mechanism needs to be further studied. Therefore, we will use the ADAM9 gene knockout mice, recombinant ADAM9 molecule, activator and inhibitor of IL-6 trans-signaling in vivo experiments. We use transgenic and RNAi technologies to up-regulate or down-regulate ADAM9 expression in stellate cells of liver in vitro experiments. We will adopt immunohistochemistry, Western blot, real-time quantitative RT-PCR, immunoprecipitation and other technologies to investigate the important roles and mechanism of IL-6 trans-signaling regulated by ADAM9 on the chemical liver injury induced by carbon tetrachloride from the molecule, cell, tissue and whole animal levels. Our research could further elucidate the mechanism of liver repair and regeneration after chemical liver injury, which will possibly provide new ideas and methods for treatment of related liver diseases.