Improving circadian rhythm disturbance reduces myocardial ischemia-reperfusion injury in diabetic rats

Abstract

Objective To investigate whether discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder. Methods The rats were injected intra-peritoneal with 1% streptozotocin(STZ) 30 mg/kg combined with high-fat and high-glucose diet to replicate diabetic model. Forty diabetic rats were randomly divided into four groups with 10 in each: sham surgery group(Sham group),ischemia-reperfusion group(I/R group), in which the left anterior descending coronary artery(LDA) was ligated for thirty minutes and reperfusion for 2 h,circadian rhythm disorder group(Crd group,24 h daily light and food),discontinuous sleep supplementation group(Dss group,every 3 hours of illumination and 1.5 hours break at night). We analyzed the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),determined serum creatine kinase-myoglobin(CK-MB) activity and cardiac troponin Ⅰ(cTnⅠ) concentrations; the expression level of BMAL1 and REV-ERBα was determined by Western blot. Results Compared to the sham group, the I/R group showed a significantly increased in myocardial infarct size, serum CK-MB activity and cTnⅠ concentration. The expression of the myocardial biological clock gene BMAL1 was down-regulated, while the expression of REV-ERBα was up-regulated(P＜0.05).Compared to the I/R group, the Crd group showed a significantly increase in myocardial infarct size, serum CK-MB activity and cTnⅠ concentration. The expression of the myocardial biological clock gene BMAL1 was down-regulated, while the expression of REV-ERBα was up-regulated (P＜0.05).Compared to the Crd group, Dss group showed a significantly decrease in the myocardial infarct size, serum cTn concentration and CK-MB activity.Furthermore,there was an increased protein expression of BMAL1 and a decrease of REV-ERBα(P＜0.05). Conclusions Discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.

Keywords

• biological clock gene|circadian rhythm disorder|diabetes|myocardial ischemia-reperfusion