miR-144通过抑制mTOR活性促进小胶质细胞自噬在脑出血炎症损伤的机制研究

项目名称： miR-144通过抑制mTOR活性促进小胶质细胞自噬在脑出血炎症损伤的机制研究

项目编号： No.81501136

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： 钟善传

作者单位： 重庆医科大学

项目金额： 17.5万元

中文摘要： 我们前期研究表明，脑出血后的代谢产物可以促进小胶质细胞自噬介导炎症反应，并且自噬关键蛋白mTOR表达下调，但其相关分子机制尚不清楚。此外，我们还发现血肿代谢产物可以诱导小胶质细胞的miRNA表达谱失衡，miR-144表达上调并诱导炎症。生物信息学分析显示：mTOR作为自噬的关键分子，可能是miR-144的靶蛋白。因此，我们推测脑出血可能通过促进小胶质细胞的miR-144表达而抑制mTOR活性，从而促进自噬介导炎症反应。本实验拟在脑出血的细胞和动物模型上，运用双荧光素酶、WB、激光共聚焦等技术，通过上调或下调miR-144，观察脑出血后小胶质细胞mTOR的变化和炎症情况。本研究将从全新的角度和思路阐明miR-144在脑出血炎症损伤的关键调控机制，深入探讨“miR-144-mTOR-自噬”的作用模式，并为miRNA在脑出血的治疗提供新的理论依据和治疗策略。

中文关键词： miR-144；mTOR；小胶质细胞；自噬；脑出血

英文摘要： Our previous study demonstrated that metabolites could promote microglia autophagy mediated inflammatory response and downregulate autophagy key protein mTOR expression after intracerebral hemorrhage. In addition, we also found that the hematoma metabolites could induce imbalance of microglia miRNA expression spectrum, miR-144 expression increased and inflammation induced. Bioinformatics analysis showed that: mTOR as key molecular autophagy, is likely to be the target protein miR-144. Therefore, we speculate that cerebral hemorrhage could promote microglia miR-144 expression and inhibit mTOR activity, thereby promote autophagy mediated inflammatory response. In this experiment, we explore the mTOR expression and inflammatory response by miR-144 expression with dual luciferase, WB and confocal laser technology assays in cell and animal models of intracerebral hemorrhage.This study will provide new insight to clarify miR-144 as key regulatory mechanism of inflammatory lesions in intracerebral hemorrhage, and explore the model of miR-144-mTOR-autophagy. In addition, the study will provide new theoretical basis and treatment strategies for intracerebral hemorrhage.

英文关键词： miR-144;mTOR;microglia;autophagy;ICH