Improving circadian rhythm disturbance reduces myocardial ischemia-reperfusion injury in diabetic rats / 基础医学与临床

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 stai-ning),determined serum creatine kinase-myoglobin(CK-MB)activity and cardiac troponinⅠ(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 ex-pression of REV-ERBα was up-regulated(P<0.05).Compared to the I/R group,the Crd group showed a signifi-cantly 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 is-chemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.