Circadian rhythm regulates Nrf2 expression in acute kidney injury following myocardial ischemia-reperfusion in rats
Objective To explore the role of brain and muscle ARNT-like protein 1(Bmal1)regulating nuclear factor erythropoietin-2-related factor 2(Nrf2)protein in acute kidney injury following myocardial ischemia-reperfusion(MIR)in rats.Methods SD rats were divided into sham group and MIR group by random number table method,8 in each group.All rats were anesthetized with pentobarbital and intubated for mechanical ventilation.The MIR model was established by occluding the left anterior descending coronary artery for ischemia(30 min),followed by removal of the microvascular clamp for 2 h of reperfusion.The ligatures were tightened at the light time point(ZT0)and the dark time point(ZT12)in both groups.Hematoxylin-eosin(HE)staining was used to evaluate myocardial and renal histological damage.Creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were detected to evaluate the degree of myocardial damage.Serum creatinine(Scr),urea nitrogen(BUN),neutrophil gelatinase-associated lipocalin(NGAL)and renal tissue superoxide dismutase(SOD)and malondialdehyde(MDA)were detected to evaluate the degree of renal damage.Western blot was used to detect the changes in Bmal1 and Nrf2 protein expression levels.Results Compared with the sham group,the MIR group had significant renal histologic changes and higher renal histologic grading scores at ZT0 and ZT12,with statistically significant differences(t=25.62,31.97;both P＜0.05);the renal histologic grading scores at ZT12 of the MIR group were significantly higher than those at ZT0(t=7.79,P＜0.05).Compared with at ZT0 in the sham group,serum CK-MB,LDH,Scr,BUN,NGAL,MDA levels were significantly higher and SOD activity was significantly lower at ZT0 of the MIR group(t=40.20,31.81,15.89,11.70,12.50,6.58,7.12;all P＜0.05);compared with at ZT12in the sham group,serum CK-MB,LDH,Scr,BUN,NGAL,MDA levels were significantly higher and SOD activity was significantly lower at ZT12 of the MIR group(t=49.33,53.61,22.90,17.20,16.82,11.23,9.96;all P＜0.05);the levels of CK-MB,LDH,Scr,BUN,NGAL and MDA at ZT12 of the MIR group were significantly higher than that at ZT0,and the activity of SOD was significantly lower than that at ZT0(t=8.07,23.41,7.76,5.38,5.68,5.16,4.05;all P＜0.05).Compared with at ZT0 in the sham group,the protein expression of Bmal1 and Nrf2 was significantly higher at ZT0 of the MIR group(t=17.80,18.14;both P＜0.05);compared with at ZT12 in the sham group,Bmal1 and Nrf2 protein expression was significantly elevated at ZT12 of the MIR group(t=13.18,13.82;both P＜0.05);Bmal1 and Nrf2 protein expression at ZT12 was significantly lower than that at ZT0 in MIR group(t=9.30,10.62;both P＜0.05).Conclusion In brief,MIR aggravated renal injury in rats at night,which was related to the decrease of Nrf2 protein regulated by Bmal1 at night.
万方数据
维普
