Ang(1-7)促进内皮细胞TERT线粒体转位减轻重症急性胰腺炎胰腺微循环障碍的作用与机制研究

胰腺微循环障碍是重症急性胰腺炎（SAP）重要发病机制，ROS损伤内皮细胞(EC)是微循环障碍的关键因素。我们研究发现Ang(1-7)减轻SAP胰腺出血、坏死等病理改变，胰腺EC存在端粒酶逆转录酶（TERT）。最新证实Ang(1-7)上调EC线粒体TERT，线粒体TERT降低ROS产生。但Ang(1-7)在SAP胰腺微循环障碍中的作用和机制尚不清楚。本研究：①Ang(1-7)干预SAP小鼠，活体微循环检测，明确Ang(1-7)减轻SAP胰腺微循环障碍的作用；②慢病毒转染干扰胰腺微血管内皮细胞TERT线粒体转位起始蛋白TOM20，探究Ang(1-7)促进TERT线粒体转位的分子机制；③Ang(1-7)干预敲低/过表达TERT的SAP小鼠和胰腺微血管内皮细胞，明确Ang(1-7)增加EC线粒体TERT减轻SAP胰腺微循环障碍的作用机制。以期为寻找SAP治疗新靶点提供实验依据。

Pancreatic microcirculatory disturbance is the key pathogenesis of severe acute pancreatitis (SAP), ROS interact with endothelial cells (EC) lead to Microcirculation disturbance is an important feature in SAP. Recent study demonstrated that Angiotensin(1-7) (Ang(1-7)) can reduce ROS by mitochondria telomerase reverse transcriptase (TERT) upregulation in EC. But the main effect of Ang(1-7) in alleviating microcirculation disturbance has not been raised and confirmed. In our present project: (1) Establish the SAP mice models and interfere them with Ang(1-7), Observe vivo microcirculation by microcirculation microscope and pathology of pancreatic tissue, so that to clarify the function of Ang(1-7) alleviate microcirculation disturbance in SAP; (2) Applying for lentivirus interfere TOM20 which is the initiating protein of TERT transposition, in order to explicit the mechanisms of Ang(1-7) to promoted TERT transposition through TOM20/TOM40/TIM23 pathway; (3) Establish TERT over express/knock down SAP modles in vivo and vitro respectively, and determine the mechanisms of Ang(1-7) increasing mitochondria TERT in EC, reducing the production of mitochondria ROS and therefore alleviate the microcirculation disturbance in SAP. Our study will provide experimental evidence for finding out new therapeutic of SAP.