Role of HDAC3 in renal injury induced by myocardial ischemia-reperfusion in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of histone deacetylase 3 (HDAC3) in renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods SPF healthy adult male Sprague-Dawley rats,weighing 210-220 g,were used in this study.Diabetes mellitus was induced by intraperitoneal injection of 1％ streptozotocin 60 mg/kg.Eighteen diabetic rats were divided into 3 groups (n =6each) using a random number table method:sham operation group (group S),group I/R and HDAC3 inhibitor RGFP966 group (RG).The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion.RGFP966 10 mg/kg was intraperitoneally injected at 1 h before myocardial ischemia in group RG.The right internal carotid artery was isolated at 120 min of reperfusion for measurement of serum lactate dehydrogenase (LDH),creatine kinase-MB (CKMB),creatinine (Cr) and urea nitrogen concentrations.Renal tissues were obtained for examination of the pathological changes and for determination of the expression of HDAC3,silent information regulator 1 (SIRT1) and interleukin-1β (IL-1β).The damage to the renal tubules was scored.Results Compared with S group,the serum LDH,CK-MB,Cr and urea nitrogen concentrations and renal tubular damage score were significantly increased,the expression of HDAC3 and IL-1β was up-regulated,and the expression of SIRT1 was down-regulated in group I/R (P＜0.05).Compared with group I/R,the serum LDH,CK-MB,Cr and urea nitrogen concentrations and renal tubular damage score were significantly decreased,the expression of HDAC3 and IL-1β was down-regulated,and the expression of SIRT1 was up-regulated in group RG (P＜0.05).Conclusion Up-regulated expression of HDAC3 is involved in renal injury induced by myocardial I/R in diabetic rats.