Recombinant mouse MANF participates in the protection of myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway
Objective To investigate the protective effect of neurotrophic factor(MANF)derived from midbrain astrocytes on myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway.Methods 48 mice were randomly divided into 4 groups:control group,recombinant mouse MANF(rmMANF)group,cecal ligation and puncture(CLP)group and CLP+rmMANF group,with 12 mice in each group.The survival rate,sepsis score,anal temperature,blood biochemical indexes,pathological indexes of myocardial injury and the expression of endoplasmic reticulum stress(ERS)related proteins were detected 8 h after CLP.H9C2 cells were divided into control group(Con),LPS group,LPS+rmMANF group,LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group.The cells were collected after 24 h treatment with LPS,and the expression of ERS protein and apoptosis in cells were an-alyzed.Results Compared with CLP group,the sepsis score and serum Lactate dehydrogenase(LDH),creatine ki-nase(CK),aspartateaminotransferase(AST)and blood urea nitrogen(BUN)levels in CLP+rmMANF group de-creased significantly(P＜0.01),and the anal temperature and serum albumin(ALB)levels increased significantly(P＜0.05).Compared with CLP group,the expression of MANF in CLP+rmMANF group increased significantly(P＜0.01),and the expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP)and the percentage of TUNEL positive cells decreased significantly(P＜0.05).In vitro,LPS stimulation down-reg-ulated the expression of SIRT1 and AMPK in H9C2 cells,while rmMANF further increased the expression level of SIRT1 and AMPK.Compared with LPS+rmMANF group,the expression of GRP78 and CHOP protein and the apop-tosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significant-ly(P＜0.05).Conclusion rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway,thereby protecting myocardial injury.
万方数据
维普
