心肌缺血再灌注过程中,lncRNA-HRIM通过靶向调节miRNA-21-5p干预细胞自噬通路的研究

在缺血再灌注（I/R）过程中，抑制过度自噬可减少心肌细胞损伤。我们前期发现在I/R过程中，心肌细胞LncRNA-HRIM表达上调，增加自噬促使细胞死亡，而miRNA-21-5p表达下调，它抑制细胞过度自噬，减少心肌细胞死亡。初步结果提示：在心肌I/R过程中，LncRNA-HRIM与miRNA-21-5p可反向调控心肌细胞自噬水平。基于此，我们假设在心肌I/R过程中，lncRNA-HRIM靶向调节miRNA-21-5p，间接调控其靶基因，干预细胞自噬通路。因此，本研究欲构建心肌I/R损伤模型，通过RNA干扰或基因过表达等手段，体内深入探讨LncRNA-HRIM和miRNA-21-5p对心肌细胞自噬水平及心梗面积的影响；同时采用荧光素酶报告基因载体、pull-down等实验阐明在自噬调控层面LncRNA-HRIM和miRNA-21-5p之间的相互作用，为心肌缺血再灌注损伤的防治提供新治疗靶点。

Excessive autophagy induced cardiac myocytes cell death during ischemia/reperfusion (I/R) period. In this study, we found that lncRNA-HRIM expression significantly upregulated in myocytes subjected to I/R, and is associated with increasing autophagy levels, which lead to enhance cell death. In contrast, miRNA-21-5p expression is significantly downregulated, and miRNA-21-5p mimic in myoctyes contributes to reduce the level of autophagy, eventually decreasing myocardial cell death in response to I/R. These preliminary results tell us that lncRNA-HRIM and miRNA-21-5p play a reverse role in regulating I/R-induced autophagy in cardiac myocytes and effect cardiac I/R injury. Based on it, we will establish a model of I/R injury in cardiac myocytes and investigate the function and mechanism of lncRNA-HRIM and miRNA-21-5p in regulating autophagy pathway of cardiac myocytes injury during I/R period using RNA interference or gene over-expression technology，and then clarify the interaction between lncRNA-HRIM and miRNA-21-5p in cardiomyocytes using luciferase assay and pull-down assay. We try to provide new therapeutic targets for the prevention and treatment of cardiac I/R injury.