miR-155对mTOR信号通路的调控在乙醇诱导的心肌胰岛素抵抗的作用及其机制

Alcoholic cardiomyopathy has become severe social problem. Alcohol consumption mediated insulin resistance is considered as important mechanism for cardiac injury. Our previous work found that long-term ethanol intake inhibits GLUT4 expression and induces insulin resistance in heart, whereas the underlying mechanism remains further investigation. MiR-155 is widely expressed in cardiac muscle and involved in multiple cardiovascular diseases. Recent evidence showed miR-155 could modulate mTOR signaling, important regulator for insulin signaling. The hypothesis is ethanol intake could modulate mTOR signaling and contribute to insulin resistance via regulating miR-155. The project aims to investigate: 1. whether miR-155 is involved in ethanol induced insulin resistance via regulating mTOR signaling; 2. whether regulating miR-155 could ameliorate ethanol mediated insulin resistance and thereby improve cardiac injury. Our research might provide novel insight into the mechanism of ethanol induced insulin resistance and new evidence for therapeutic targeting alcoholic cardiomyopathy.

酒精性心肌病已成为严重的社会问题。目前认为，饮酒诱导的心肌胰岛素抵抗是心肌损伤的重要机制。项目组前期工作发现，长期饮酒可抑制心肌GluT4表达，诱导心肌胰岛素抵抗，但是具体机制有待进一步研究。miR-155是心肌中广泛表达的一种microRNA，与多种心血管疾病的发生发展密切相关。新近研究发现，miR-155对mTOR信号通路具有修饰作用。mTOR是目前已知的胰岛素信号的重要调节因子。饮酒是否通过miR-155，进而影响心肌mTOR信号通路诱导胰岛素抵抗，目前还不清楚。本项目拟采用体内体外实验相结合的方法，重点探讨两方面问题：1, miR-155对mTOR的调控作用是否参与了饮酒诱导的心肌胰岛素抵抗发生。2，干预miR-155能否改善饮酒诱导的心肌胰岛素抵抗和心肌损伤。该研究一方面可以有助于深化目前对于饮酒诱导心肌胰岛素抵抗的认识，另一方面也可为临床寻找酒精性心肌病的干预靶点进行有意探索。