论文部分内容阅读
Objective: To observe the role of activation of aldehyde dehydrogenase 2 (ALDH2) on myocardial ischemia/reperfusion injury in diabetic rats, and investigate the related mechanism.Methods: Diabetic rat model was simulated by intraperitoneal injection 55 mg/kg STZ and divided into diabetic and diabetic+ethanol (the agonist of ALDH2) groups.Eight weeks after modeling, myocardial I/R was mimicked ex vivo, and divided into control I/R, diabetic +I/R (DM+I/R);diabetic + ethanol +I/R (DM+EtOH+I/R);diabetic + ethanol +cyanamide +I/R (DM+EtOH+CYA+I/R);diabetic + ethanol +atractyloside+I/R (DM+EtOH+Atr+I/R) and diabetic + ethanol +wortmannin +I/R (DM+EtOH+Wor+I/R) groups.Results: In contrast to I/R in control rat, in diabetic rat, LVDP,+dp/dtmax and RPP during reperfusion period were decreased, LVEDP was increased, LDH release in coronary flow was increased, ALDH2 activity, mRNA and ALDH2 protein levels were significantly decreased, Caspase-3,Caspase-8 and Caspase-9 activities were increased.Compared with DM+I/R group, in DM+EtOH+I/R group,LVDP, ±dp/dtmax and RPP were increased, LVEDP was decreased;LDH release was increased, ALDH2 activity,mRNA and ALDH2 protein levels were increased, Caspase-3, Caspase-8 and Caspase-9 activities were decreased.Compared with DM+EtOH+I/R group, in DM+EtOH+CYA+I/R, DM+EtOH+Atr+I/R and DM+EtOH+Wor+I/R groups, LVDP, ±dp/dtmax and RPP were further decreased, and LVEDP was increased.LDH release was increased,ALDH2 activity, mRNA and ALDH2 protein levels were significantly decreased, Caspase-3, Caspase-8 and Caspase-9 activities were increased.Conclusions: In diabetic rats, ALDH2 expression was decreased when heart was subjected to I/R.Activation of ALDH2 plays myocardial protective and anti-apoptosis role through inhibiting the ooening of mitoPTP and activation of PI3K-Akt signaling pathway.