人脐带MSC来源exosome介导miR-181c调控严重烧伤过度炎症反应的机制研究

项目名称： 人脐带MSC来源exosome介导miR-181c调控严重烧伤过度炎症反应的机制研究

项目编号： No.81501694

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李晓

作者单位： 中国人民解放军总医院

项目金额： 18万元

中文摘要： 严重烧伤引起的过度炎症反应常导致多器官功能障碍、脓毒症，甚至患者死亡。研究表明 MSC-exosome可在多种疾病中发挥抗炎作用。我们前期研究发现①人脐带MSC-exosome可降低巨噬细胞内TLR4、NF-κB/P65等炎症相关蛋白表达、减轻巨噬细胞炎症活化；②人脐带MSC-exosome内含有miR-181c，且miR-181c在烧伤后大鼠体内表达明显降低。TLR4是miR-181c的潜在作用靶点，人脐带MSC-exosome是否通过miR-181c抑制TLR4炎症信号通路发挥抗炎作用目前尚无报道。本课题拟从分子、细胞及动物水平研究人脐带MSCs-exosome介导miR-181c下调TLR4蛋白表达在严重烧伤过度炎症反应中的作用和分子机制，为人脐带MSCs-exosome调控严重烧伤过度炎症反应提供一种新思路，也为烧伤患者的临床诊治、预后判断提供新的生物学靶点。

中文关键词： 烧伤；炎症反应；间充质干细胞；exosome；微小RNA-181c

英文摘要： Excessive inflammation caused by severe burns often leads to multiple organ dysfunction syndrome, sepsis, and even result in death. Mesenchymal stem cell-derived exosomes (MSC-exosome)play important roles in reduce inflammation in several diseases. We have previously found that ：①human umbilical cord MSC(hUCMSC)-exosome reduced macrophage inflammation, and decresed level of TLR4、NF-κB/P65. ②miR181c is contained in hUCMSC-exosome which significantly decreased in sever burn mice. hUCMSC-exosome and miR181c involved in severe burns excessive inflammation has not been reported before. TLR4 act as a potential targets of miR181c, but there is no report about hUCMSC-exosome and miR-181c in TLR4 signal pathway. Our study proposed by cell model, animal model and clinical samples to investigate hUCMSC-exosome mediated miR181c decreased TLR4 protein expression in severe burns excessive inflammation. Our project will open a nevol avenue for molecular mechanism of hUCMSC-exosome in excessive inflammatory, and provide a new candidate marker for diagnosis and therapeutic target for severe burn excessive inflammation patients.

英文关键词： burn;inflammation;Mesenchymal stem cells;exosome;miRNA-181c