Effects of sufentanil on cardiac function and apoptosis of myocardial cells in rats with acute myocardial infarction based on Fas/FasL signaling pathway
Objective To explore the effects of sufentanil on cardiac function and apoptosis of myocardial cells in rats with acute myocardial infarction(AMI)based on fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods Totally 108 healthy male SD rats were randomly divided into the control group,model group,low-dose sufentanil group,high-dose sufentanil group,high-dose sufentanil +Fas negative control group,high-dose sufentanil + Fas lentivirus group,with 18 rats in each group.In the model group,low-dose sufentanil group,high-dose sufentanil group,high-dose sufentanil + Fas negative control group,high-dose sufentanil + Fas lentivirus group,we established AMI models by ligation of left anterior descending branch of coronary artery;the steps of the control group were the same as those of AMI model except that the left anterior descending coronary artery was not lapped.Rats in the low-dose sufentanil group and high-dose sufentanil group were intraperitoneally injected with 0.1 and 1 μg/kg sufentanil,respectively.After AMI models were successfully made,rats in the high-dose sufentanil + Fas negative control group and high-dose sufentanil + Fas lentivirus group were injected with 1 μg/kg sufentanil intraperitoneally,200 nmol/kg NC shRNA lentivirus or 200 nmol/kg Fas lentivirus intravenously,respectively;while rats in the control group and model group were intraperitone-ally injected with the same amount of normal saline.The tail venous blood of rats was collected at 72 h after operation,and the serum troponin T was detected by ELISA.Left ventricular ejection fraction(LVEF),left ventricular shortening frac-tion(LVFS),left ventricular end-diastolic diameter(LVEDd)and left ventricular end-systolic diameter(LVESd)were measured by echocardiography.After the cardiac function of the rats was detected,blood was collected from the abdominal aorta and serum TNF-α and IL-6 were detected by ELISA.All the rats were decapitated and their hearts were taken,the heart tissues of six rats were randomly collected and TTC staining was performed to detect the myocardial infarction size;the cardiac tissues of six rats was randomly selected,HE staining was used to observe the pathological changes of myocardial tissues,and apoptosis was detected by TUNEL method;the expression levels of apoptosis-related proteins Bcl-2,Bax,Caspase-3 and Fas/FasL signaling pathways were detected in the heart tissues of the remaining six rats by Western blot-ting.Results Compared with the control group,the serum troponin T level increased,LVEDd and LVESd increased,LVEF and LVFS decreased,serum TNF-α and IL-6 levels increased,myocardial infarction area increased,apoptosis rate and protein expression levels of Bax,Caspase-3,Fas and FasL increased,Bcl-2 protein expression decreased in the model group(all P＜0.05).Compared with the control group,the myocardial cells in the model group were blurred,the texture disappeared,the arrangement was disordered,the small blood vessels between the myocardium were dilated,the number of cells decreased,and a large number of inflammatory cells infiltrated.Compared with the model group,serum troponin T level,LVEDd and LVESd decreased,LVEF and LVFS increased,serum TNF-α and IL-6 levels decreased,and myocardial infarction size decreased,the apoptosis rate and the expression levels of Bax,Caspase-3,Fas and FasL decreased,while the expression of Bcl-2 increased in the low-dose sufentanil group and high-dose sufentanil group(all P＜0.05).Compared with the model group,the morphology,texture,arrangement,vasodilation,cell number and inflammatory cell infiltration of cardiomyocytes in the low-dose and high-dose sufentanil groups were significantly improved.Compared with the high-dose sufentanil + Fas negative control group,serum troponin T level,LVEDd and LVESd increased,LVEF and LVFS decreased,serum TNF-α and IL-6 levels increased,myocardial infarction size increased,the apoptosis rate and the expression levels of Bax,Caspase-3,Fas and FasL increased,while the expression of Bcl-2 decreased in the high-dose sufentanil + Fas lentivirus group(all P＜0.05).Compared with the high-dose sufentanil + Fas negative control group,the cardiomyocytes in high-dose sufentanil + Fas lentivirus group had blurred morphology,disappeared texture,disordered arrangement,dilated small blood vessels between myocardium,reduced cell number,and obvious inflammatory cell infil-tration.Conclusion Sufentanil can improve cardiac function and inhibit myocardial cell apoptosis in AMI rats,and the effect of 1 μg/kg sufentanil is better than that of 0.1 μg/kg sufentanil.Inhibition of Fas/FasL signaling pathway may be one of its mechanisms.
国家科技期刊平台
NSTL
万方数据
维普
