肝纤维化是多种慢性肝病发展至肝硬化的重要中间环节，阻断其发生发展是防治慢性肝病的重要手段之一。我们的前期研究表明乏氧微环境可明显加重肝纤维化程度，与HSC线粒体自噬密切相关，鳖甲煎丸可通过抑制HIF-1α表达达到抗肝纤维化的目的。因此本研究进一步提出，HIF-1α可能通过PINK1/Parkin信号轴调控HSC线粒体自噬影响HSC活化，鳖甲煎丸通过干预其调控过程，改善肝脏气滞血瘀乏氧微环境达到抗肝纤维化的目的。本项目拟以HSC、HIF-1α基因敲除小鼠肝纤维化模型为研究对象，采用基因编辑、透射电镜，免疫荧光共定位等技术，首先探讨HIF-1α调控HSC线粒体自噬激活HSC的作用机制，进一步明确鳖甲煎丸通过抑制HIF-1α蛋白表达抗肝纤维化的作用途径及靶点，从益气活血化瘀、改善肝脏乏氧微环境等方面阐明其抗肝纤维化的科学内涵，同时对深化肝纤维化气滞血瘀证微观物质基础研究具有重要理论意义。

Liver fibrosis is an important intermediate link in the process of the development of various chronic liver diseases to cirrhosis. Blocking its development and progression is one of the important means to prevent and treat chronic liver diseases. Our previous studies revealed that hypoxic microenvironment will aggravate the degree of liver fibrosis significantly, which is closely related to mitochondrial autophagy of HSC. Biejiajian pills can act as an anti-liver fibrosis drug by inhibiting the expression of HIF-1α. Therefore, we further suggested that HIF-1α may regulate HSC mitochondrial autophagy through the PINK1 / Parkin signal axis and affect HSC activation. Biejiajian pills can prevent liver fibrosis by intervening in the above regulation process, relieving the liver Qi-stagnation and blood stasis, and improving hypoxia microenvironment. Here, we intend to take the HSC and HIF-1α gene knockout mouse model of liver fibrosis as the research object, to explore the role of HIF-1α in regulating mitochondrial autophagy and activating of HSC, and to further clarify the pathways and targets of Biejiajian pills in the process of resisting liver fibrosis by inhibiting the expression of HIF-1α protein with the use of gene editing, transmission electron microscopy, immunofluorescence co-localization and other technologies, as well as to clarify the scientific connotation of anti-hepatic fibrosis effects from the aspects of tonifying Qi, promoting blood circulation and removing blood stasis, and improving the liver hypoxic microenvironment, etc. which has important theoretical significance for deepening the basic research of microscopic material foundation for Qi-stagnation and blood stasis syndrome of liver fibrosis at the same time.