基于lncRNA 探讨针刺抗MCAO大鼠脑缺血后神经血管单元损伤的作用机制研究

项目名称： 基于lncRNA 探讨针刺抗MCAO大鼠脑缺血后神经血管单元损伤的作用机制研究

项目编号： No.81503647

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： 尤艳利

作者单位： 中国人民解放军第二军医大学

项目金额： 18万元

中文摘要： 缺血性脑卒中病理机制尚未完全阐明。针对脑缺血病理损伤中的某个靶点开发的治疗候选药物的临床疗效均不理想，寻找新的治疗靶点是提高临床疗效的关键。lncRNAs在肿瘤、神经退行性疾病中的作用引起高度关注，并取得了一定成果，但在缺血性脑卒中的研究相对较少。课题组前期研究表明针刺治疗脑缺血有较好的疗效。本研究拟采用高通量测序方法检测MCAO模型大鼠脑组织lncRNAs的表达及其针刺对其干预效应，运用GO分析、KEGG分析等方法对lncRNA的表达谱进行分析，通过权重基因共表达网络分析法构建差异基因的lncRNAs-mRNAs共表达网络，并运用RT-PCR技术对差异表达2-5倍以上的4-6个lncRNAs进行验证，从细胞生物学调控网络角度深入阐释脑缺血后脑损伤发生的病理机制及针刺保护NVU的可能物质基础及有效作用靶点。本研究将有助于揭示针灸治疗脑缺血的效应机制，为针刺治疗脑缺血提供客观的实验与理论依据

中文关键词： 针刺研究；脑缺血；水沟穴；长链非编码RNA；作用机制

英文摘要： The pathological mechanism of ischemic stroke has not been fully elucidated. The.most disporting is the failure of clinical trials of candidate drugs designed by targeting one of the pathological injury mechanisms．So the search for new therapeutic targets is the key to improve the clinical efficacy. The role of lncRNA in tumor, neurodegenerative disease have attracted much attention, and the study achieved some results. Comparing with tumor and neurodegenerative disease，study of IncRNAs in post-ischcmia is very limited. Previous studies show that there is good curative effect of acupuncture in treating cerebral ischemia..This study Use the Rat IncRNA microarray to observe the IncRNAs expression profile of ischemia rat brains and to evaluate the therapeutic effects of acupuncture in the Middle cerebral artery occlusion model(MCAO) in rats, Use bioinformatics techniques(KEGG pathway analysis and GO analysis) analyze the microarray results，construct the lncRNAs-mRNAs co-expression network with Weighted Correlation Network Analysis , and use RT-PCR to verify the differential expression 4-6 lncRNAs >2-5 folds, to find the possible lncRNAs which may play the roles in multi-pathological pathway, and Regulative action of acupuncture on it.From the cell biological regulatory networks we will thoroughly explanate the mechanisms of brain injury after cerebral ischemia, the material basis and effective target of acupuncture protecting neurovascular unit(NVU). This study will help to reveal the mechanism of acupuncture for treatment of cerebral ischemia, and provide objectively theoretical and experimental basis for acupuncture treatment of cerebral ischemia.

英文关键词： acupuncture;cerebral ischemia;Shuigou;long non-coding RNA;mechanism