FTO介导的RNA m6A去甲基化修饰在丘脑出血卒中后中枢痛中的作用及机制研究

卒中后中枢痛(CPSP)是一种中枢性神经病理性疼痛综合征。丘脑出血是CPSP的重要病因之一。由于对CPSP发病机制的认识存在严重不足，目前临床上尚无行之有效的治疗手段。RNA m6A修饰作为基因表达调控新方式，其生物学意义尚未完全阐明。最近研究发现，RNA m6A修饰失调会导致一些生理缺陷，并参与一些神经系统疾病的病理过程，但关于m6A修饰在CPSP中的机制研究仍然知之甚少。我们前期发现RNA去甲基化酶FTO在丘脑出血后中枢痛的发生发展过程中扮演重要角色，并且预实验结果提示FTO可以调控Nlrp3 mRNA的去甲基化修饰。随后，我们通过生信分析预测及实验验证发现调控FTO的上游信号分子：转录因子Runx1。但其具体调控机制尚不十分清楚。因此，本项目拟在此基础上，通过小鼠丘脑出血后中枢痛模型，围绕Runx1-FTO-NLRP3轴深入研究CPSP的关键分子机制，为临床防治CPSP提供理论基础。

Central post-stroke pain（CPSP） is a type of central neuropathic pain syndrome. Thalamic hemorrhage is one of the important causes of CPSP. Because of the lack of understanding of the pathogenesis of CPSP, there is no effective treatment, currently. RNA m6A is the most common modification method in eukaryotic mRNA. M6A modification is a new pattern to regulate gene expression, and its biological significance has not been fully elucidated. Recently, some studies have shown that dysregulation of RNA m6A modification can cause some physiological defects and RNA m6A modification participated in the pathological process of some neurological diseases. However, little is known about the mechanism of m6A modification in CPSP. Our previous research found that RNA demethylase FTO plays an important role in the occurrence and development of CPSP after thalamic hemorrhage, and pre-experimental results suggest that FTO can regulate Nlrp3 mRNA demethylation modification. Subsequently, we found the upstream signaling molecule that regulates FTO: the transcription factor Runx1. However, its specific regulation mechanism is not very clear. Therefore, this project intends to further study the key molecular mechanism of Runx1-FTO-NLRP3 signal axis in a mouse CPSP model induced by thalamic hemorrhage to provide a theoretical basis for clinical prevention and treatment of CPSP.