循环微囊泡中miRNA参与调控机体多种病理生理过程。我们前期研究发现：风湿性心脏病（RHD）大鼠心瓣膜及血液Th17细胞效应因子升高，且循环微囊泡中miR-155表达升高，用RHD大鼠微囊泡干预体外培养的Th17细胞，细胞S1PR1蛋白表达水平下调，而pSTAT3蛋白表达水平上调。已有研究表明S1PR1/STAT3通路与Th17细胞分化密切相关。我们推测，微囊泡中miR-155可能通过下调S1PR1基因，激活STAT3信号，促进Th17细胞分化，参与RHD发生发展。本课题拟将miR-155模拟物或抑制物导入微囊泡中，用其干预Lewis大鼠及体外诱导分化的Th17细胞，并采用靶基因验证、慢病毒载体转染大鼠及细胞、免疫印迹及流式细胞等技术，阐明循环微囊泡中miR-155靶向S1PR1/STAT3通路调节Th17细胞在风湿性心脏病中的作用，为防治RHD提供新的理论依据及干预靶点。

Circulating microvesicles-mediated miR-155 involve in regulating a variety of pathophysiological processes in the body. Our previous studies have shown that Th17 cells effectors increased in the cardiac valves and blood of RHD rats. Circulating microvesicles-mediated miRNAs from RHD rats also increased. After interfering Th17 cells with microvesicles from RHD rats in vitro, as a result the S1PR1 protein was downregulated and pSTAT3 protein was upregulated in these Th17 cells.Existing researches have shown S1PR1/STAT3 signal pathway was closely related to Th17 cell differentiation. So we speculate that circulating microvesicles-mediated miR-155 may downregulates S1PR1 genes and activates STAT3 signal pathway, so as to promote Th17 cell differentiation in the development of RHD. In this study, miR-155 mimics and inhibitors will be transfered into microvesicles ,which will be used to intervene the Lewis rats and induce Th17 cells differentiation in vitro. And validation of target genes, lentiviral vector transfection to rats and cells, flow cytometry, western blot will be used in this research to clarify that the role of circulating microvesicles mediated miR-155 targeting S1PR1/STAT3 signal pathway to regulate Th17 cells in rheumatic heart disease,so as to lay new theoretical foundations and intervention targets for the prevention and treatment of RHD.