Recombinant mouse MANF participates in the protection of myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway
10.19405/j.cnki.issn1000-1492.2024.11.013
- Author:
Hao He
1
;
Cheng Li
1
;
Sai Hu
1
;
Fengqiang Xia
1
;
Chi Zhang
1
;
Jing Wang
1
Author Information
1. Dept of Critical Care Medicine , Changsha Fourth Hospital (Changsha Hospital Afiliated to Hunan Normal University) , Changsha 410006
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum stress;
mesencephalic astrocyte-derived neurotrophic factor;
sepsis;
myocardial injury
- From:
Acta Universitatis Medicinalis Anhui
2024;59(11):1981-1988
- CountryChina
- Language:Chinese
-
Abstract:
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 analyzed.
Results:Compared with CLP group, the sepsis score and serum Lactate dehydrogenase(LDH),creatine kinase(CK),aspartateaminotransferase(AST) and blood urea nitrogen(BUN) levels in CLP+rmMANF group decreased 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-regulated 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 apoptosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significantly(P<0.05).
Conclusion:rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway, thereby protecting myocardial injury.
- Full text:2024122613463892746重组鼠MANF通过激活SI...毒症诱导心肌损伤的保护作用_何浩.pdf
