肝肺综合征（HPS）机制不明、防治困难，针对其核心改变“肺血管新生”的病理进程进行干预是防治研究的新策略。在前期预实验中我们发现，肺微血管内皮细胞（PMVECs）极性迁移对HPS肺血管新生进程至关重要，同时细胞极性蛋白par3低表达可能是促进PMVEC“极性迁移”的关键靶点。我们提出“肝病通过多种细胞因子/血流动力学改变作用于肺→PMVECs细胞-细胞连接处par3表达减弱→VE-cadherin-par3-Tiam1复合物破坏→Tiam1从胞膜异位到胞质→Rac1异常激活→细胞间连接减弱、微丝细胞骨架重塑→细胞极性迁移→肺血管新生→HPS”。为此，本课题拟建立HPS在体和离体模型，采用基因转染、荧光成像、免疫共沉淀等技术，阐明肺血管新生过程中细胞极性迁移的具体调控机制。为制定以par3为靶点，抑制PMVECs极性迁移以获得更佳治疗HPS新策略奠定理论基础。

Poorly defining the mechanisms responsible for pulmonary angiogenesis results in no effective medical therapies of hepatopulmonary syndrome (HPS). In the preliminary study we found that the polarized migration of pulmonary microvascular endothelial cells (PMVECs) play an important role in the pathogenesis of lung angiogenesis, meanwhile the low expression of cell polarity protein par3 may be the key target for the promotion of "polarized migration" of PMVECs. And then, we propose that "the liver disease through a variety of cytokines / hemodynamic changes act on lung → the low expression of par3 in cell-cell junctions of PMVECs → VE-cadherin-par3-Tiam1 composite damage → Tiam1 from cell membrane to cytoplasm → ectopic activation of Rac1 → cell-cell junctions weakened and microfilament cytoskeleton remodeling → cell polarized migration → lung angiogenesis → HPS". In this study, the HPS rat and PMVECs model will be established, gene transfection, fluorescence imaging, Co-IP will be applied to clarify the specific regulation mechanism of cell polarized migration in the pathogenesis of pulmonary angiogenesis of HPS, to explore whether Par3 as a target to inhibit PMVECs polarized migration is a new therapeatic strategies for HPS treatment.