Role of TIPE2 in sepsis-induced myocardial injury in mice: the relationship with AKT/GSK-3β/β-catenin signaling pathway
10.3760/cma.j.cn131073.20230512.00918
- VernacularTitle:TIPE2在小鼠脓毒症心肌损伤中的作用：与AKT/GSK-3β/β-catenin信号通路的关系
- Author:
Qian WANG
1
;
Yuxuan WANG
;
Tingqian MING
;
Zhenshuai JIN
;
Min YUAN
;
Qian KONG
;
Xiaojing WU
Author Information
1. 武汉大学人民医院麻醉科，武汉 430060
- Keywords:
Protein-serine-threonine kinases;
Glycogen synthase kinase 3 beta;
beta Catenin;
Sepsis;
Myocardial injury;
Tumor necrosis factor-alpha-induced protein-8 l
- From:
Chinese Journal of Anesthesiology
2023;43(9):1113-1116
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2(TIPE2) in sepsis-induced myocardial injury and the relationship with serine-threonine kinase(AKT)/glycogen synthase kinase-3β(GSK-3β)/β-catenin signaling pathway in mice.Methods:Sixteen male wild-type C57BL/6N mice and 16 TIPE2-gene knockout C57BL/6N mice, aged 6-8 weeks, with a body mass index of 20-25 g, were divided into 4 groups using a random number table method: wild-type+ sham operation group(group WT-sham), wild-type+ cecal ligation and perforation(CLP) group(group WT-CLP), TIPE2-gene knockout sham operation group(group KO-sham) and TIPE2-gene knockout CLP group(group KO-CLP), with 8 mice in each group. The model of myocardial injury induced by sepsis was developed by CLP in anesthetized animals. Blood samples from the inferior vena cava were collected at 24 h after surgery for determination of the concentrations of cardiac troponin I(cTnI) in serum by enzyme-linked immunosorbent assay. Then the mice were sacrificed and myocardial tissues were collected for determination of the pathological changes(by hematoxylin and eosin staining), expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 mRNA(by quantitative polymerase chain reaction), and expression of TIPE2, phosphorylated AKT(p-AKT), phosphorylated GSK-3β(p-GSK-3β) and β-catenin(by Western blot).Results:Compared with the corresponding Sham groups, the serum cTnI concentration was significantly increased, the expression of TNF-α, IL-1β and IL-6 mRNA and expression of p-AKT, p-GSK-3β and β-catenin in myocardial tissues were up-regulated, the expression of TIPE2 was down-regulated( P<0.05), and the pathological changes of myocardium were found in corresponding CLP groups. Compared with group WT-CLP, the serum cTnI concentration was significantly increased, the expression of TNF-α, IL-1β and IL-6 mRNA and expression of p-AKT, p-GSK-3β and β-catenin in myocardial tissues were up-regulated, the expression of TIPE2 was down-regulated( P<0.05), and the pathological changes of myocardium were aggravated in group KO-CLP( P<0.05). Conclusions:TIPE2 reduces the myocardial injury probably through inhibiting the AKT/GSK-3β/β-catenin signaling pathway in septic mice.
