circRNA调控心肌梗死后心肌细胞焦亡的分子网络及干预研究

细胞焦亡是一种由炎症反应引起的细胞程序性死亡。新近研究发现心肌梗死时局部炎症可导致心肌细胞的焦亡，因此抑制焦亡有望成为心肌梗死治疗的新方向，但心肌细胞焦亡的分子机制仍不清楚。CircRNAs是一类环状结构的非编码RNA，已证实与多种疾病发生密切相关。在前期研究中我们通过芯片筛选发现circRNA-30287在心肌梗死边缘区组织中显著上调，且其表达水平与caspase-1和GSDMD表达呈正相关，提示其是心肌细胞焦亡的重要调控因子。本课题拟运用分子克隆、Luciferase等技术验证（1）circRNA-30287是否调控心肌梗死时心肌细胞焦亡的发生；（2）揭示circRNA-30287通过靶向调控miRNAs-CASP1/GSDMD分子网络诱导心肌细胞焦亡；（3）circRNA-30287是否可以成为心肌保护的新靶点。本研究将发现抑制心肌细胞焦亡的新靶点，将为临床心肌梗死的防治提供新思路。

Pyroptosis is a new type of programmed cell death caused by inflammation. Recent studies uncovered that the inflammation in myocardial infarction may lead a large number of myocardial cell to pyroptosis, and thus inhibiting pyroptosis is expected as the new direction of the treatment of myocardial infarction. But the molecular mechanism of cardiomyocyte pyroptosis is still not clear. CircRNAs is one kind of non-coding RNA with cyclic structure, which has been proved to be closely related to many diseases. In the preliminary study, we found that circRNA-30287 was significantly upregulated in infarcted tissues by microarray screening, and its expression was positively correlated to focal pyroptosis factors caspase-1 and GSDMD expression, suggesting that circRNA-30287 as an important factor for myocardial pyroptosis. This project will employ molecular cloning, luciferase and other methods to verify: (1) whether circRNA-30287 is involved in the regulation of cardiomyocyte pyroptosis in myocardial infarction; (2) revealed that circRNA-30287-miRNAs-CASP1/GSDMD signal pathway mediates cardiomyocyte pyroptosis; (3) whether circRNA-30287 will become a new target for myocardial protection. In this study, we will find a new target to inhibit the pyroptosis of myocardial cells, so as to reduce the occurrence of serious complications such as heart failure after myocardial infarction.