Midazolam alleviates myocardial ischemia-reperfusion injury by regulating hippopotamus/Yes-associated protein signaling pathway
Objective To investigate the effects of midazolam(MDZ)on myocardial ischemia-reperfusion injury(MIRI)in rats by regulating the hippopotamus(Hippo)/Yes-associated protein(YAP)signaling pathway.Methods Forty-eight rats were randomly divided into four groups with 12 rats in each group.The MIRI rat model was constructed by ligation of the anterior descending branch of the left coronary artery in three groups,and then the three groups were randomly assigned to receive normal saline(10 mL/kg),MDZ(0.1 mg/kg),Fasudil hydrochloride(10 mg/kg),this formed the MIRI group,MDZ group,and Fasudil hydrochloride group.The other group only underwent operation without ligation assigned to receive normal saline(10 mL/kg)formed the sham group.Serum levels of creatine kinase isoenzyme(CK-MB),cardiac troponin I(cTnI),lactate dehydrogenase(LDH),malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor(TNF-α)and interleukin-1β(IL-1β)were detected by enzyme linked immunosorbent assay.Triphenyltetrazolium chloride staining,hematoxylin eosin staining,and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to examine myocardial infarction area,myocardial histopathological changes,and cardiomyocyte apoptosis.The expression of YAP target genes connective tissue growth factor(CTGF)and cysteine-rich protein 61(CYR61)mRNA was detected by qPCR.Western blot was used to detect the expression of cleaved cysteine aspartate proteinase 1(cleaved Caspase-1)and ratios of phosphorylated(p)-large tumor suppressor kinase 1(LATS1)/LATS1,p-YAP/YAP,p-mammalian sterile 20-like kinase 1(MST1)/MST1.Results Compared with the sham group,CK-MB,cTnI,LDH,MDA,TNF-α,IL-1β,myocardial infarction area,cardiomyocyte apoptosis rate,cleaved Caspase-1,p-LATS1/LATS1,and p-YAP/YAP were increased in MIRI group,while CTGF,CYR61 mRNA expression,p-MST1/MST1,and SOD level were decreased(P＜0.05).Compared with the MIRI group,the CK-MB,cTnI,LDH,MDA,TNF-α,IL-1β,myocardial infarction area,cardiomyocyte apoptosis rate,cleaved Caspase-1,p-LATS1/LATS1,and p-YAP/YAP in MDZ group and Fasudil hydrochloride group were decreased,CTGF,CYR61 mRNA expression,p-MST1/MST1,and SOD level were increased(P＜0.05).Conclusion MDZ may activate the Hippo/YAP signaling pathway,inhibit oxidative stress and inflammatory responses,reduce apoptosis in cardiomyocyte,and improve myocardial injury in MIRI rats.
万方数据
维普
