ASSA13-03-28 Effect of ALDH2 on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats and Related Mechanism Research

Abstract

Objective To observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion injury in diabetic rats, and study the relationships of ALDH2, PI3K-Akt and mitochondrial permeability transition pore in myocardial injury. Methods Diabetic rat model was simulated by intraperitoneal injection 55 mg/kg streptozotocin (STZ) and divided into diabetes and ethanol + diabetes groups. After 8 weeks, myocardial ischemia/reperfusion model was mimicked in vitro, and subjected to drug intervention, divided into: diabetic I/R + ethanol +cyanamide (DM +EtOH I/R +CYA); diabetic I/R + ethanol +atractyloside (DM+EtOH I/R+Atr), diabetic I/R + ethanol +wortmannin (DM+EtOH I/R+Wor). The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) content in coronary flow were determined. SOD activity and MDA content were evaluated, the activities of caspase-3 and ALDH2 were evaluated, and the expressions of Bcl-2, Bax and ALDH2 mRNA were detected by RT-PCR; ALDH2 protein expression was evaluated by western blot. Results In contrast to I/R in control rat, left ventricular development pressure (LVDP), maximal rise/fall rate of left ventricular pressure (± dp/dtmax), left ventricular work (RPP), SOD and ALDH2 activities were decreased in diabetic rat, left ventricular end diastolic pressure (LVEDP), LDH release, caspase-3 activity and MDA content were increased, and the expression of Bcl-2/Bax mRNA, ALDH2 mRNA and protein expressions were decreased. Compared with DM I/R group, in DM+EtOH I/R group, LVDP, ± dp/dtmax, RPP, SOD and ALDH2 activities were increased, LVEDP, LDH release, caspase-3 activity and MDA content were increased, and the expression Bcl-2/Bax mRNA, ALDH2 mRNA and protein expressions were increased. Compared with DM+EtOH I/R group, in DM+EtOH+CYA I/R group, DM+EtOH+Atr I/R group and DM+EtOH+ Wor I/R group, LVDP, ±dp/dtmax, RPP, SOD and ALDH2 activities were further decreased, and LVEDP, caspase-3 activity and MDA content were increased, and the expression Bcl-2/Bax mRNA, ALDH2 mRNA and protein expressions were decreased. Conclusions Enhanced mitochondrial ALDH2 expression in diabetic rats can play cardiac protective role, and activation of ALDH2 plays the myocardial protective effect through inhibiting mitoPTP opening and activation of PI3K-Akt signalling pathway.