miRNA-424 调节细胞周期对缺血脑损伤的作用及机制

项目名称： miRNA-424 调节细胞周期对缺血脑损伤的作用及机制

项目编号： No.81201028

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 赵海苹

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 脑卒中是高致残率、致死率的疾病，寻找其治疗靶点一直是缺血性卒中临床基础研究的主要目标。microRNAs在血清/血浆中稳定存在，近来已成为多种疾病的生物标志物和治疗靶点，但目前仅有少数miRNAs在脑缺血中的作用得到阐明。我们前期临床实验发现，miRNA-424在急性脑梗死患者外周血白细胞中显著减低；在小鼠脑缺血模型中发现，miRNA-424在缺血脑组织皮层中呈逐步降低的趋势；结合小鼠脑组织原位杂交结果分析，miRNA-424可能直接或间接参与了缺血脑损伤病理过程的调节。本项目拟利用动物和细胞模型，明确miRNA-424在缺血脑组织中表达和分布变化的时间规律；证实miRNA-424在脑缺血神经元损伤和神经功能障碍的作用；从明确miRNA-424对脑缺血后神经元、小胶质细胞的细胞周期的作用入手，明确其调节的靶基因，阐明其作用及机制，为急性缺血性卒中的早期治疗提供新的靶点。

中文关键词： 脑缺血；小胶质；炎症；神经元；氧化应激

英文摘要： Ischemic stroke is burdened with a high morbidity and mortality in our society. The major target of clinical and basic research in cerebral ischemia is searching for new therapeutic target. MicroRNAs (miRNAs) are small (typically ≈22 nt in size) regulatory RNA molecules that function to modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. The miRNAs are detectable and stable in human peripheral blood, and are considered to be new biomarkers and therapeutic targets for neurodegenerative diseases. However, only few miRNAs are functionally demonstrated in the cerebral ischemia. In our previous clinical research, the expression of miRNA-424 is significantly decreased in the circulating leukocytes of patients with acute cerebral infarction. And further in the mouse model of focal cerebral ischemia, miRNA-424 is also gradually reduced in the ipsilateral cortex at 4h, 8h and 24h after ischemia. Based on the above results and the in situ hybridization analysis of miR-424 on aldult mouse brain, we proposed that miRNA-424 might directly or indirectly participate in the pathology of acute cerebral ischemia. The present study is aiming to clarify the time-dependent expression pattern of miRNA-424 by using the animal and cell models, and further dem

英文关键词： Cerebral ischemia；microglia；inflammation；neuron；oxidative stress