Effect Of Irbesatan On Ischemia Reperfusion Cardiomyocyte Apoptosis And ERK1/2Pathway In Rats

objectiveTo observe the effect of pretreatment with Irbesatan on ischemiareperfusion myocardial cell apoptosis in rats,and research the relationbetween this effect and ERK1/2pathway in rats.Method54healthy male SD rats (weight250--300g) were divided randomly into5Groups:①sham operation group(n=6): not ligation the left anterior descendingcoronary artery (LAD), and observe150minutes.②ischemia reperfusiongroup(n=12): subject to30min of ischemia followed120min reperfusion.③ischemic preconditioning group(n=12): subject to5min of ischemia followed5min reperfusion, and repeated3times, the rest of the operation are the samewith ischemia reperfusion group④Irbesatan group (n=12):After1weeklavage with Irbesatan, rats were subjected to30min of ischemia followed120min reperfusion.⑤Irbesatan+PD-98059(PD)group(n=12): PD-98059wasinjected from tail vein15min before reperfusion. After reperfusion, infarct sizewere measured after dyeing by TTC; myocardial structure under lightmicroscopy by HE dyeing; apoptosis index was detected by TUNEL; theexpression of Bcl-2and Bax detected by immunohistochemistry and p-ERKlevel were measured by Western Blot. Results1. The effect of Irbesatan on infarct size: Compared with ischemiareperfusion group, infarct size are significantly decreased in ischemicpreconditioning group and Irbesatan group (P<0.01); The infarct size in PDgroup is between the ischemia reperfusion group and the Irbesatan group.2. The effect of Irbesatan on myocardial structure: The myocardial celldamage severely in Ischemia reperfusion group by HE dyeing, muscle fibersswelling Severely, Cell gap widened, Interstitial edema; Compared withischemia reperfusion group, The ischemic preconditioning group and Irbesatangroup alleviate significantly; The degree of injury in PD group is between theischemia reperfusion group and the Irbesatan group.3. The effect of Irbesatan on apoptosis index: Compared with ischemiareperfusion group, apoptosis index are significantly decreased in ischemicpreconditioning group and Irbesatan group (P<0.01); The apoptosis index in PDgroup is between the ischemia reperfusion group and the Irbesatan group.4. The effect of Irbesatan on the expression of Bcl-2and Bax: Comparedwith ischemia reperfusion group, Bax expression are significantly decreased inischemic preconditioning group and Irbesatan group, Bcl-2expression areincreased(P<0.01); Compared with Irbesatan group, Bax expression aresignificantly increased in PD group,and Bcl-2expression are decreased(P<0.01).5. The effect of Irbesatan on p-ERK level: Compared with ischemiareperfusion group, p-ERK level are increased in ischemic preconditioning groupand Irbesatan group (P<0.01); Compared with Irbesatan group, p-ERK level aredecreased in PD group (P<0.01).Conclusions1. Irbesatan can inhibit myocardial cell apoptosis in rats, decreasemyocardial infarction area, and attenuated myocardial ischemia reperfusion injury.2. These cardioprotective effects of Irbesatan are attributed mainly toactivate ERK1/2pathway,then inhibits the expression Bax,and promotes theexpressionof Bcl-2.