关键词: sirt1, 心肌缺血再灌注损伤, 内质网应激, 凋亡, ERK通路

Abstract: Objective To investigate the role silent information regulator 1 on endoplasmic reticulum dependent apoptosis pathway induced by myocardial ischemic reperfusion and the relationship with ERK1/2 pathway.Methods rats were divided into 6 groups:Control group,ischemic/reperufuison group,resverotrol treatment group, resverotrol plus EX527(1μg/kg) treatment group, resverotrol （10mg/kg）plus PD98059 (0.3mg/kg) treatment group,PD98059 treatment group,each group n=12.The myocardial I/R injury model in rats was established by ligating left anterior descending coronary artery.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 sirt1,caspase-12,CHOP, phosphor-ERK1/2 and total ERK1/2 were measured by westernblot.Results 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 while the protein expression of SIRT1 and phosphor-ERK1/2 were increased in resveratrol treatment group .Then treated with SIRT1 inhibitor EX527 in Res+EX+I/R group the increase or decrease result of those index were conteracted compared with Res+I/R group. Conclusion SIRT1 can protect heart from ischemic reperfusion injury through inhibiting ER-dependent apoptosis protein expression,the mechanism of which is partly has some relationship with ERK1/2 pathway activation.

Key words: Sirt1 , Myocardil ishcmeic reperfusion injury, endoplasmic reticulum, apoptosis, ERK1/2 pathway