miR-182调控松果体Clock基因介导缺氧缺血性脑损伤后节律紊乱的新机制

项目名称： miR-182调控松果体Clock基因介导缺氧缺血性脑损伤后节律紊乱的新机制

项目编号： No.81471488

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 冯星

作者单位： 苏州大学

项目金额： 73万元

中文摘要： 缺氧缺血性脑病(HIBD)患儿常遗留昼夜节律紊乱，严重影响患儿生存质量。我们前期芯片筛选发现:HIBD后大鼠松果体中miR-182表达明显升高。生物信息学预测其下游靶基因之一是Clock基因。而我们同时发现：HIBD后大鼠松果体Clock基因表达显著降低。Clock是昼夜节律生物钟系统中核心的、高保守的功能基因，因此我们设想：松果体中miR-182对Clock的调控可能是导致HIBD后节律紊乱的新机制。本研究拟探讨：①大鼠HIBD后松果体中miR-182与钟基因表达水平与昼夜节律的变化；②miR-182过表达/表达沉默对原代松果体细胞的影响；③大鼠体内模型研究miR-182对松果体Clock调控的机制研究。该机制尚未见报道，具有源头创新性，为HIBD防治提供新靶标。

中文关键词： 缺氧缺血性脑病；生物节律；微小RNA；发病机制

英文摘要： Hypoxic-ischemic brain damage (HIBD) survivals often suffer from circadian rhythm disorders, which substantially affect their life qualities. The underlying mechanisms for such disorders remain largely unknown. Our high-throughput screening data indicated that miR-182, a microRNA, is significantly up-regulated in rat pineal gland after HIBD. Bioinformatics analysis predicted its downstream target as the Clock gene, which was confirmed by the luciferase reporter system. Clock gene plays an important role in circadian clock system. Combining with our findings that the expression of Clock gene in pineal gland was significantly decreased after HIBD, we hypothesized that the impairment of the clock gene expression mediated by miR-182 led to the disorder of circadian disorder. To test this, we will first measure changes of miR-182 and clock gene expression after HIBD. We will then test the effects on pineal function when miR-182 is overexpressed or silenced. We will also study the relationships between miR-182, Clock gene and pineal function after HIBD. Our study therefore provides new potential therapeutic target for circadian disorders after HIBD.

英文关键词： Hypoxic-ischemic brain damage;circadian clock;microRNA;mechanism