Effect of SAHA on sufentanil postconditioning-induced cardioprotection in rats with type 2 diabetes mellitus / 中华麻醉学杂志

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 tablesham 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-I/R,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),and no significant change was found in the parameters mentioned above in T2DM-SA and T2DM-SP groups (P＞0.05).Compared with group T2DM-SP,the ±dp/dt was significantly increased,the 1S and IS/LVM ratio were significantly decreased,and the expression of myocardial p-GSK-3β was significantly upregulated in group T2DM-SASP (P＜0.05).Conclusion SAHA can improve cardioprotection induced by sufentanil postconditioning to some extent in the rats with T2DM.