Effect of SAHA on sufentanil postconditioning-induced cardioprotection in rats with type 2 diabetes mellitus

Abstract

Objective To investigate the effect of suberoylanilide hydroxamic acid(SAHA)on sufentanil postconditioning-induced cardioprotection in rats with type 2 diabetes mellitus(T2DM). Methods Male SPF Sprague-Dawley rats, weighing 250-300 g, aged 5-6 weeks, were used in the study.T2DM was induced by high-fat diet (4 weeks) and intraperitoneal 1% streptozotocin 35 mg/kg, and confirmed by fasting blood glucose level≥16.7 mmol/L.Forty rats with T2DM were divided into 5 groups(n=8 each)using a random number table: sham operation group(grou T2DM-S); ischemia-reperfusion group(group T2DM-I/R); sufentanil postconditioning group(group T2DM-SP); SAHA group(group T2DM-SA); SAHA plus sufentanil postconditioning group(group T2DM-SASP). In T2DM-SA and T2DM-SASP groups, SAHA 25 mg/kg was injected intraperitoneally once a day for 5 consecutive days before operation.Their hearts were excised and retrogradely perfused in a Langendorff apparatus.The hearts were subjected to 30 min of global ischemia followed by 120 min of reperfusion to establish the model of ischemia/reperfusion injury.At 30 min of equilibration and 30, 60 and 120 min of reperfusion, the left ventricular systolic pressure(LVSP), heart rate(HR), and the maximum rate of increase and decrease of ventricular pressure(±dp/dtmax)were recorded.At 120 min of reperfusion, the left ventricular mass(LVM)and infarct size(IS)were measured, and IS/LVM ratio was calculated.The expression of glycogen synthesis kinase 3β(GSK-3β)and phosphorylated GSK-3β(p-GSK-3β)in the myocardium was detected by Western blot. Results Compared with group T2DM-S, the LVSP, HR and ±dp/dtmax were significantly decreased, the IS and IS/LVM ratio were significantly increased, and the expression of myocardial p-GSK-3β was significantly down-regulated in group T2DM-I/R(P 0.05). Compared with group T2DM-SP, the ±dp/dtmax was significantly increased, the IS and IS/LVM ratio were significantly decreased, and the expression of myocardial p-GSK-3β was significantly up-regulated in group T2DM-SASP(P<0.05). Conclusion SAHA can improve cardioprotection induced by sufentanil postconditioning to some extent in the rats with T2DM. Key words: Hydroxamic acids; Diabetes mellitus, type 2; Sufentanil; Myocardial reperfusion injury