乙型肝炎病毒致肝脏慢性炎症和细胞癌变的具体机制目前仍未明确，乙肝病毒X蛋白（HBx）在此过程中发挥关键作用。课题组前期研究首次证实了细胞色素C氧化酶亚单位III（COXIII）是HBx的体内结合蛋白，COXIII在维持线粒体正常功能中发挥重要作用。本课题将在共聚焦显微镜下观察HBx同COXIII结合后线粒体超微结构的改变，检测HBx对COXIII质子传递功能及细胞色素C氧化酶功能的影响，观测由此诱发的线粒体通透性转换孔（MPTP）开放造成细胞内钙超载所带来线粒体功能的级联损害，评估人肝细胞和小鼠肝脏组织在HBx作用下炎症损伤指标。使用HBx siRNA和MPTP特异性抑制剂-环孢素A阻断HBx的作用，再次评估以上指标的改变。本课题将有助于深入阐明HBx导致肝细胞炎症损伤的过程和机制，为针对HBx的相关治疗开创新思路。

HBV X protein(HBx), a viral protein encoded by HBV, is essential for HBV replication and acts as a key factor in the development of inflammatory injury and hepatocarcinoma induced by HBV. However, the mechanism and details of HBx on inflammatory injury in human hepatocytes, which may also be a main reason for oncogenesis of hepatocarcinoma, remain unclear. Our previous study had reported the finding of a new HBx-interacting protein,cytochrome c oxidase subunit III(COXⅢ) which is important for mitochondrial function, by yeast two hybrid system. This achievement builds the basement of follow-up researches for HBx pathogenetic mechanism. In this study, a confocal microscopy will be used to observe the functional location of HBx interacting with COXIII in innermembrane of mitochondria and the ultrastructual changes caused by interaction between HBx and COXIII. A complex mixed by cytochrome c oxidase and liposome will mimic cytochrome c oxidase in mitochondrial membrane in hepatocytes,so the proton pump function of COXIII can be studied in a relatively independent way.The purified HBx will be added to the complex to inhibit proton pump function of COXIII. Cytochrome c oxidase function interferred by HBx will also be examined in both the complex and hepatocytes. The open of mitochondria permeability transition pore(MPTP) will be measured by detection of calcium level in human hepatocytes with or without HBx expression.The function injury of mitochondria will be examined as a comprehesive one, distinguished from respectively independent function of COXIII, cytochrome c oxidase and MPTP. Inflammatory changes in both human hepatocytes and mouse liver will be assessed as final evaluations for injury caused by HBx. A HBx siRNA and Cyclosporin A which is a specific inhibitor for MPTP will be applied to reverse the inflammatory injury induced by HBx. This study is designed to give an interpretation for the mechanism of inflammatory injury induced by HBx in human hepatocytes，and will make HBx a target for treatment of patients with HBV infection.