AP-2α调控间充质干细胞表达SDF-1/CXCR4参与肝肺综合征病理性肺血管新生的作用及机制研究

肝肺综合症（HPS）病死率高、防治困难，近年报道发现病理性肺血管新生在HPS的发生发展中起到重要作用。AP-2α是转录因子AP-2家族中的重要一员,与细胞生长、分化和凋亡都有密切的联系。其是否通过SDF-1/CXCR4信号轴调控BM-MSCs功能从而参与HPS血管新生是我们要探索的关键问题。前期发现HPS大鼠外周血中MSCs的数量明显升高并且MSCs在CBDL大鼠血清的刺激下SDF-1/CXCR4表达升高，同时通过生物信息学的预测和生物芯片的分析发现AP-2α在HPS大鼠肺组织中表达增高并可能结合到SDF-1/CXCR4的启动子序列上。本课题拟建立大鼠HPS和MSCs模型, 采用流式细胞术、染色质免疫沉淀、荧光素酶报告基因、定量PCR、重组腺病毒转染和siRNA等技术，阐明AP-2α调控MSCs表达SDF-1/CXCR4在HPS病理性肺血管新生中的作用，从而为HPS治疗新策略奠定理论基础。

Hepatopulmonary syndrome (HPS) has a high fatality rate and results in no effective medical therapies. Recent researches have reported that pulmonary pathological angiogenesis plays a vital role in the development of HPS. AP-2α is a transcription factor that belongs to the AP-2 family and it has a close relationship with cell growth、differentiation and apoptosis. Whether SDF-1/CXCR4 signal axis takes part in the HPS angiogenesis is a key problem that we will study. Our previous study found the number of peripheral blood MSCs（mesenchymal stem cell，MSCs）was obviously increased in HPS rats and the cultured MSCs which were stimulated by CBDL serum expressed more SDF-1 and CXCR4. Furthermore, the analysis of bioinformatics and biochip results indicated that AP-2α was highly expressed in lung tissues of HPS rat and it may bind to the promoter sequence of SDF-1 and CXCR4. In this study, models of HPS and MSCs will be established. Flow cytometry, chromatin immunoprecipitation, luciferase reporter gene, real-time PCR, Recombinant adenovirus transfection and siRNA will be applied to identify the role of AP-2α regulating the expression of SDF-1/CXCR4 in MSCs invovled in the HPS pulmonary angiogenesis and develop new therapeutic strategies for HPS treatment.