长链非编码RNA-RP11-402L1.1通过自噬通路调控减少心肌缺血再灌注损伤的研究

缺血再灌注引起心肌细胞过度自噬致细胞死亡。我们研究发现在再灌注损伤过程中，抑制细胞过度自噬可减少心肌细胞损伤。近年研究提示LncRNAs的表达失调在疾病发生发展中扮演重要角色。本研究前期工作应用microarray芯片，完成心肌细胞缺血再灌注损伤后lncRNAs的差异表达，并根据生物信息学分析挑选出LncRNA-RP11-402L1.1进行细胞生物学功能研究。已发现抑制心肌细胞LncRNA-RP11-402L1.1水平可减少细胞LC3及Caspase3表达，同时减少心肌细胞死亡。初步结果提示缺血再灌注过程中LncRNA-RP11-402L1.1可调控心肌细胞自噬和凋亡水平，减轻心肌细胞损伤。故在此基础上构建缺血再灌注损伤模型，通过RNA干扰和基因过表达等手段，探讨LncRNA-RP11-402L1.1在缺血再灌注过程中调控心肌细胞自噬的作用及其机制，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 our pilot experiments, we found that the inhibition of excessive autophagy level reduced cardiac myocytes cell death from I/R injury. Recently, increasing evidences showed the disorders of long non-coding RNAs (lncRNAs) expression play an important role in the development of many diseases. In this study, we had screened the differences of lncRNAs expression using Microarray Analysis in myocardial cells subjected to I/R. And we selected lncRNA-RP11-402L1.1 for further study according to the results of the bioinformatics analysis. Of note, our data demonstrated that the suppression of the lncRNA-RP11-402L1.1 level reduced the expression of LC3 and Caspase 3, eventually decreasing myocardial cell death in response to I/R. These preliminary results tell us that lncRNA-RP11-402L1.1 may play an potential role in regulating I/R-induced autophagy and apoptosis in cardiac myocytes and mitigate 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-RP11-402L1.1 in regulating autophagy pathway of cardiac myocytes injury during I/R period using RNA interference and gene over-expression technology. We try to provide new therapeutic targets for the prevention and treatment of cardiac I/R injury.