The Effect Of Sirt1 On Endoplasmic Reticulum Realated Apoptosis During Myocardial Ischemic/Reperfusion In Rat And The Role Of Erk1/2 Pathway

Objective:To investigate the role of silent information regulator 1 (SIRT1) on endoplasmic reticulum dependent apoptosis pathway induced by myocardial ischemic reperfusion(I/R) and the relationship with extracellular signal-regulated kinase 1/2 (ERK1/2)signal pathwayMethods:Seventy-two male Sprague-Dawle rats were divided into 6 groups(n= 12):Control group,ischemic/reperufuison group(I/R group),resverotrol treatment group(Res+I/R group), resverotrol plus EX527(1 μg/kg) treatment group(Res+EX+IR group), resverotrol (10mg/kg) plus PD98059 (0.3mg/kg) treatment group(Res+PD+IR group),PD98059 treatment group(PD+IR group).The myocardial I/R injury model in rats was established by ligating left anterior descending coronary artery,the drugs were administrated through caudal vein.TUNEL method was used to detect myocardial apoptosis; Colorimetric method was used to measure LDH and CK-MB activity.qRT-PCR was used to detect the myocardial mRNA expression of GRP78,caspase-12 and CHOP;The protein expression of sirtl,caspase-12,CHOP, phosphor-ERK1/2 and total ERK1/2 were measured by westernblotResult1.Compared with I/R group,the myocardial cell apoptosis index,LDH and CK-MB activity,mRNA expression of GRP78,caspase-12,CHOP and the protein expression of caspase-12,CHOP were decreased in resveratrol treatment group (P<0.05).Then treated with SIRT1 inhibitor EX527 decrease result of those index were conteracted compared with Res+I/R group.2.Compared with I/R group, the protein expression of SIRT1 and phosphor-ERK1/2 were increased in Res+I/R group (P<0.05).While decreased in Res+EX527+I/R group compared with Res+I/R group (P<0.05).Conclusion:1.SIRT1 can protect heart from ischemic reperfusion injury through inhibiting ER-dependent apoptosis protein expression.2.The mechanism of which has some relationship with ERK1/2 pathway activation.