解毒化瘀II方对ACLF大鼠外泌体miR-21/CCL20/IL-17通路的调控效应机制研究

已有研究证实过表达miR-21可下调CCL20、IL-17表达，抑制炎症，CCL20是miR-21的靶基因；但外泌体miR-21/CCL20/IL-17通路在ACLF中的发病机制尚有待阐明。项目组前期研究提示解毒化瘀Ⅱ方能下调IL-17，抑制炎症，具有免疫调控及保护作用。据此我们认为：解毒化瘀Ⅱ方可能通过过表达外泌体miR-21/CCL20/IL-17通路来调控ACLF的疾病进程及临床结局。该项目拟通过构建ACLF大鼠模型，采用WB、miRNA芯片、慢病毒载体构建及转染等实验技术来揭示外泌体miR-21/CCL20/IL-17通路在ACLF大鼠中的免疫调控效应，并相继阐明解毒化瘀II方对其的调控靶点，为ACLF的中医药临床治疗服务。该项目一旦完成，将为ACLF新的发病机制阐发及治疗干预手段更新提供更有力的科学证据，为中医药治疗疑难重症的有益尝试走向世界打开一扇崭新的窗口。

It has been confirmed that overexpression of miR-21 can down regulate the expression of CCL20 and IL-17 and inhibit inflammation. CCL20 is the target gene of miR-21. However, the pathogenesis of exocrine miR-21 / CCL20 / IL-17 pathway in ACLF remains to be elucidated. The preliminary study of the project group suggested that Jiedu Huayu Ⅱ could down regulate IL-17, inhibit inflammation, and have immunomodulatory and protective effects. Therefore, we believe that Jiedu Huayu Ⅱ formula may regulate the disease process and clinical outcome of ACLF by over expression of exocrine miR-21 / CCL20 / IL-17 pathway. This project intends to reveal the immunomodulatory effect of exocrine miR-21 / CCL20 / IL-17 pathway in ACLF rats by constructing ACLF rat model, using WB, miRNA chip, lentivirus vector construction and transfection and other experimental techniques, and successively clarify the regulation target of Jiedu Huayu II formula for ACLF clinical treatment by traditional Chinese medicine. Once the project is completed, it will provide more powerful scientific evidence for the elucidation of the new pathogenesis of ACLF and the renewal of treatment interventions, and open a new window to the worldfor the beneficial attempt of traditional Chinese medicine in the treatment of difficult and severe cases .