Role Of Homer 1a In Non-infarcted Areas Ventriclar Remodeling After Myocardial Ischemia/reperfusion In Type2 Diabetic Rats

Objective:Diabetic patients with coronary heart disease have a mortality accounts for almost 50%,which is 2 to 4 times compare with the non-diabetic patients.By means of thrombolytic therapy or percutaneous coronary intervention(PCI) and other means to restore coronary blood flow promptly and effectively is the best strategy to relieve the myocardial injury caust by myocardial infarction.However,the ischemia/reperfusion(IR)injury cost by such reperfusion will further damage the myocardium and finally increase the infarct size.Ischemic preconditioning(IPC) has the strongest myocardial protective effect in the endogenous protective mechanisms. But a large number of studies have confirmed that in diabetic patients or model,the protective effect of IPC is not as obviously as in patients or model without diabetic.ERK is belong to the reperfusion injury salvage kinase(RISK), in hypertrophic cardiomyocytes, the upregulation of Homer 1a can interfere the activation of ERK. This study try to expression the Role of Homer 1a in non-infarcted areas ventriclar remodeling after myocardial ischemia/reperfusion in diabetes.Methods:(1) By established the type 2 diabetes rat model and the model of type 2 diabetic rat with myocardial infarction and ischemia/reperfusion model, then used commercial antibodies to detected the expression of Homer 1a in rat myocardial cells.(2) H9C2 cells were cultured by high glucose and insulin, and analogged the ischemia by removed the medium and oxygen at the same time. Then observed that high glucose and insulin whether induce the Homer 1a expression in H9C2 cells, as well as ischemia/reperfusion.(3) Synthesized si RNA against Homer 1a to knockout the expression of Homer 1a. Homer1 a knockout cells were cultured with high glucose and insulin, then were given ischemia/reperfusion treatment. Used flow cytometry to detecte Cell apoptosis.(4) Cultured H9C2 cells which transfected with si RNA in high glucose and insulin, and then they were given the ischemia/reperfusion treatment, then detect ANP expression.(5) After silenced Homer 1a, observed how high glucose and insulin or ischemia/reperfusion to induced ERK1/2 phosphorylation,Result:(1) In the non-infarcted areas, diabetes, myocardial infarction and myocardial ischemia/reperfusion could induce upregulation of Homer 1a expression in myocardial cells. And in diabetic rats, the upregulation was more obviously.(2) High glucose and insulin could induce the upregulation of Homer 1a expression in H9C2 cells, as well as ischemia/reperfusion. And in the cells cultured with high glucose and insulin, the upregulation of Homer 1a induced by ischemia/reperfusion was more obviously.(3) Apoptosis rate was in si RNA cells, lower than nc RNA cells, suggesting that Homer 1a upregulation enhanced high glucose and insulin and ischemia/reperfusion induced apoptosis.(4) ANP expression level in si RNA group was higher than ncRNA group, suggested that the uprefulation of Homer 1a may inhibit the myocardial hypertrophy in non-infarcted area ventricular reconstruction after diabetic myocardial ischemia/reperfusion.(5) None of high glucose and insulin or ischemia/reperfusion could upregulat the expression of Homer 1a, high glucose and insulin or ischemia/reperfusion could induced ERK1/2 phosphorylation, and in Homer 1a silent H9C2 cells, the activation level of ERK1/2 was more significant.Conclusion: In short, the above studies show that diabetes and diabetic patients with myocardial ischemia/reperfusion could upregulate the expression of Homer 1a in myocardial cells. This upregulation inhibit the activation of ERK1/2, and promote the apoptosis of myocardial cells. Meanwhile, due to the inhibition of ERK1/2 activation, it reduced the cardiomyocyte hypertrophy in non-infarcted area ventricular remodeling after the diabetic myocardial ischemia / reperfusion.