基于circDnajc1/miR-27a-5p/C1qc信号轴探讨小胶质细胞活化在缺血性中风神经元凋亡中的作用及桃红四物汤调控机制

缺血性中风（IS）是人类致残和致死的主要原因之一，但其确切机制不明。CircRNAs参与IS病理过程。课题组研究显示circDnajc1是IS发病关键circRNA，可结合miR-27a-5p而上调C1表达，促进炎症反应，桃红四物汤对其具有调控作用。故我们提出“MCAO/R和OGD/R模型中circDnajc1可竞争性结合miR-27a，上调C1qc表达，诱导小胶质细胞活化，引起神经元凋亡”的假说。本课题以前期研究为基础，ceRNA理论为依据，circDnajc1为切入点，circDnajc1/miR-27a-5p/C1qc信号轴为主线，MCAO/R大鼠和小胶质细胞OGD/R为模型，桃红四物汤为干预手段，从“整体→器官→细胞”不同层次探讨circDnajc1/miR-27a-5p/C1qc信号轴参与IS发病的机理及桃红四物汤的调控机制，探索其防治新靶点，为中医药防治IS提供新思路和新策略。

Ischemic stroke (IS) is one of the main causes of human disability and death, but the exact mechanism is unknown. More and more studies have suggested that circRNAs are involved in IS pathology. Our preliminary studies found that circDnajc1 is a key circRNA in the pathogenesis of IS. It can be combined with miR-27a-5p to up-regulate the expression of C1 and promote the inflammatory response. Taohong Siwu Decoction can regulate it. Therefore, we propose the hypothesis that the circDnajc1 can competitively bind miR-27a in MCAO / R and OGD / R models, upregulate C1qc expression, induce microglial activation, and cause neuronal apoptosis. This project is based on previous research and ceRNA theory, circDnajc1 is the entry point, circDnajc1 / miR-27a-5p / C1qc signal axis is the main line, MCAO / R rats and microglia OGD / R are models, Taohong Siwu Decoction is a means of intervention, exploring the mechanism of circDnajc1 / miR-27a-5p / C1qc signal axis participating in the pathogenesis of IS and the regulation mechanism of Taohong Siwu Decoction from different ways. This project will provides potential therapeutic targets for IS and new research ideas for Chinese medicine.