miR-21-5p及miR-21-3p共调控在创伤性血脑屏障损伤修复中的作用及机制研究

项目名称： miR-21-5p及miR-21-3p共调控在创伤性血脑屏障损伤修复中的作用及机制研究

项目编号： No.81501055

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： 葛歆瞳

作者单位： 天津医科大学

项目金额： 17.5万元

中文摘要： 创伤性血脑屏障（BBB）损伤是脑外伤（TBI）后脑组织病变进展的关键环节。申请人前期发表的成果表明（最高影响因子5.078）：TBI后，miR-21-5p主要在神经元中产生抗细胞凋亡作用，并间接促进BBB损伤修复。此外也发现：miR-21-3p（与miR-21-5p同时由miR-21前体产生）可能通过调控脑微血管内皮细胞血管生成因子的表达，减轻BBB渗漏。为全面研究miR-21在创伤性BBB损伤修复中的作用及机制，本研究拟通过TBI大鼠模型及体外实验：1.明确miR-21-3p在创伤性BBB损伤修复中的作用；2.探明miR-21-3p通过调控血管生成因子的表达，影响下游免疫炎症反应及细胞凋亡，进而产生上述作用的机制；3.探明miR-21-5p及3p共调控在创伤性BBB损伤修复中的作用及机制。本研究将进一步阐明TBI后BBB损伤修复的病变机制，为探索miRNA治疗TBI的新策略提供理论依据。

中文关键词： 颅脑创伤；miR-21-5p；miR-21-3p；血脑屏障；血管生成因子

英文摘要： The traumatic blood-brain barrier (BBB) damage is an important pathological change in brain after traumatic brain injury (TBI). In our previous papers (highest impact factor: 5.078), we have reported that miR-21-5p in neurons can exert an anti-apoptosis effect, and promote the restoration of injured BBB after TBI. In addition, we found that miR-21-3p, which is generated from pre-miR-21 at the same time with miR-21-5p, may possibly reduced the BBB leakage through regulating the expression of angiogenic factors in brain microvascular endothelial cells. Based on these findings, experiments on TBI rats and in vitro cultured cells are designed to comprehensively study the function and mechanism of miR-21-3p in the restoration of traumatic BBB damage. The objectives of our proposed research include: 1. Prove the function of miR-21-3p in the restoration of traumatic BBB damage; 2. Clarify the possible mechanism that miR-21-3p exerted above function through regulating the expression of angiogenic factors, thus impacting the downstream immuno-inflammatory responses and cellular apoptosis; 3. Clarify the co-regulative function and mechanism of miR-21-5p and miR-21-3p in the restoration of traumatic BBB damage. The outcome of this research will further elucidate the mechanism of BBB damage and restoration after TBI. It will also provide insights into developing a novel therapeutic strategy of miRNA therapy for TBI.

英文关键词： Traumatic Brain Injury;miR-21-5p;miR-21-3p;Blood-Brain Barrier;Angiogenic Factors