高迁移率家族蛋白B1介导特异性microRNAs对隐球菌脑膜炎后血脑屏障通透性的调控

项目名称： 高迁移率家族蛋白B1介导特异性microRNAs对隐球菌脑膜炎后血脑屏障通透性的调控

项目编号： No.81501039

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： 刘玲娟

作者单位： 中南大学

项目金额： 17.5万元

中文摘要： 隐球菌性脑膜炎是儿童较常见的中枢神经系统感染性疾病，在早期极易误诊和漏诊，且具有较高的病死率。高迁移率家族蛋白B1是一种高度保守的染色体结合蛋白，本研究组证实了其与受体RAGE的结合激活Cdc42途径，导致血脑屏障通透性发生改变，加剧隐球菌脑膜炎。当前已有大量研究证实在miR-294、-22、-200c、-218、-181、-155、-181a的3’-UTR区均存在HMGB1结合位点，通过负调控HMGB1的蛋白表达调控细胞的增殖及代谢过程。因此，本项目组拟在此基础上探索特异性miRNAs是否通过作用于HMGB1的表达影响隐球菌脑膜炎后血脑屏障通透性。拟采取整体动物及体外人脑血管内皮细胞为研究目标，应用瞬时转染、Western blot、实时定量PCR等技术检测特异性miRNAs是否参与了隐球菌脑膜炎的病理过程及HMGB1是否介导了该过程的调控，以期从崭新的角度探究隐球菌脑膜炎的治疗靶点

中文关键词： 隐球菌脑膜炎；microRNA；血脑屏障；高迁移率家族蛋白B1

英文摘要： Cryptococcal meningitis, a common central nervous system infectious diseases for children, is easy to misdiagnosis and misdiagnose at early stage, and has a high mortality. High mobility family protein B1 is a kind of highly conservative chromosome binding protein, our study has confirmed that it regulated the blood brain barrier (BBB) permeability through the combination with RAGE receptor then activated Cdc42. Currently studies have demonstrated that there were binding cite on the 3’-UTR region of miR-294, - 22, -200c, -218, -181, -155, -181 for HMGB1, regulated the process of cellular proliferation and metabolic through negative regulation of HMGB1 protein expression. Therefore, our study proposed to explore whether specific miRNAs impacts on the blood brain barrier permeability after cryptococcal meningitis by acting on the expression of HMGB1.Take the whole animal and human vascular endothelial cells in vitro as the research target, we use several experimental method, such as transient transfection, Western blot and real time quantitative PCR techniques and so on, to detecte the alteration of specific miRNAs expression which involved in the pathological process of cryptococcal meningitis, and then explore whether HMGB1 mediates this process, in order to from a new perspective to explore the treatment targets for cryptococcal meningitis.

英文关键词： Cryptococcal meningitis ;microRNA;Blood-brain barrier;High mobility family protein B1