lipid raft/caveolae调节PMVECs接触性抑制在肝肺综合症肺微血管扩张中的作用和机制研究

肝肺综合症（HPS）是由慢性肝病引起的肺血管并发症,其主要病理变化特征是肺内微血管扩张（IPVD），我们的前期研究证实肺微血管内皮细胞（PMVECs）发生异常增殖和肌样分化,从而加重IPVD进展。研究中我们发现HPS大鼠血清刺激PMVECs由单层向复层生长，HPS大鼠肺微血管管壁增厚，难以用增殖和分化解释，提示可能存在明显的接触性抑制减弱，有望成为HPS防治的新靶点。鉴于lipid raft/caveolae在接触性抑制中起重要作用，本课题拟建立在体和离体模型，观察HPS时PMVECs中lipid raft/caveolae接触性抑制相关蛋白表达变化；构建Ad-intergrin载体，破坏脂质筏，siRNA技术干预caveolin，检测肺微血管管壁变化及上述蛋白表达变化，以阐明lipid raft/caveolae 调节细胞接触性抑制在HPS中IPVD中的作用，为HPS的防治提供新思路.

Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication caused by chronic hepatosis,a key pathophysiological component of which is IPDV.Our previous study comfirmed that the abnormal proliferation and myogenic differentiation of PMVECs aggravated the progression of IPVD.We found that HPS rat serum stimulated PMVECs stratified growth from signal-layer,and pulmonary microvascular wall of HPS rat thickened, which could not be explained by proliferation and differentiation and indicate an obvious attenuation of contact inhibition and may become a new target of HPS treatment. Since lipid raft/cavelae play an important role in contact inhibiton, we plan to structure in vivo and in vitro HPS model to observe the expressions of contact inhibtion-related proteins in lipid raft/caveolae of PMVECs;construct Ad-intergrin vectors,disrupt lipid raft and apply siRNA to knockdown caveolin to detect the changes of microvascular wall and related protein expression. Therefore, elucidate the role of lipid raft/caveolae regulating contact inhibition in IPVD of HPS，and provide a new insight in prevention and treatment of HPS.