Role of HDAC3 in renal injury induced by myocardial ischemia-reperfusion in diabetic rats

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=6 each) 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 (CK-MB), 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. Key words: Histone deacetylases; Diabetes mellitus; Myocardial reperfusion injury; Acute kidney injury