Protective effect and mechanism of overexpression of BMAL1 on muscle injury in sepsis mice
Objective:To explore the effect of circadian clock gene aromatic hydrocarbon receptor nuclear trans-port-like protein 1(BMAL1)overexpression on mitochondrial autophagy pathway in myocardial injury of sepsis mice.Methods:Forty mice were randomly divided into model control group,model group,negative control(NC)group and BMAL1 group,with 10 mice in each group.Left ventricular short-axis shortening rate(LVFS),left ven-tricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVIDd),left ventricular end-systolic diam-eter(LVIDs)were detected by echocardiography in mice,serum creatine kinase isoenzyme(CK-MB)and troponin I(cTnI)were detected by ELISA,pathological changes of myocardial tissue were observed by HE staining,myocardi-al apoptosis was detected by TUNEL staining,the ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy,the expression levels of microtubule-associated protein 1 light chain 3(LC3),BH3-domain autophagy protein(Beclin1),PTEN-induced kinase(Pink1),E3 ubiquitin-ligase active Parkinson's disease protein 2(Parkin)and voltage-dependent anion channel protein 1(VDAC1)in myocardial tissue were de-termined by Western blotting.Results:Compared with model group and NC group,LVFS and LVEF in BMAL1 group were increased(P＜0.05),LVIDd and LVIDs were decreased(P＜0.05),serum CK-MB and cTnI were de-creased(P＜0.05),myocardial tissue lesions were improved,the rate of TUNEL positive cells was decreased(P＜0.05),the damage to mitochondria was reduced,LC3Ⅱ/LC3Ⅰ ratio in myocardial tissue was further increased(P＜0.05),and Beclin1,Pink1,Parkin and VDAC1 protein expression levels were further up-regulated(P＜0.05).Conclusion:Overexpression of BMAL1 can significantly improve cardiac function and alleviate myocardial injury in sepsis mice,which may be related to the promotion of mitochondrial autophagy.
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NSTL
万方数据
维普
