Effects of cardiomyocyte-specific TSHR knockout on myocardial insulin resistance in mice with heart failure
10.3760/cma.j.cn311282-20250108-00012
- VernacularTitle:心肌细胞特异性敲除TSHR对心力衰竭小鼠心肌胰岛素抵抗的影响研究
- Author:
Yanlong YANG
1
;
Xiao LU
;
Ziqi HAN
;
Leyuan ZHANG
;
Limin TIAN
Author Information
1. 甘肃中医药大学第一临床医学院，兰州 730000
- Publication Type:Journal Article
- Keywords:
Thyroid-stimulating hormone;
Insulin resistance;
Heart failure
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(5):411-416
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of cardiomyocyte-specific TSHR knockout on myocardial insulin resistance in a mouse model of heart failure.Methods:A cardiomyocyte-specific TSHR knockout(TSHR CKO) mouse model was generated by crossing TSHR flox/flox mice with α-MHC-Cre transgenic mice. F1 offspring(TSHR flox+ /-α-MHC-Cre+ mice) were interbred to obtain TSHR CKO mice, and littermate TSHR flox/flox mice served as controls. Fasting blood glucose levels were measured using a Roche glucometer, and fasting insulin levels were determined using a mouse insulin ELISA kit. Cardiac function and the expression of ANP, BNP, β-MHC, IRS-1, IRβ, GLUT-4, phosphorylated IRS-1, phosphorylated IRβ, and TSHR in myocardial tissues were assessed by echocardiography, RT-qPCR, Western blot, and immunohistochemistry(IHC). IHC was also used to evaluate the myocardial expression of IRS-1 and GLUT-4, while Masson′s trichrome staining was performed to assess the degree of myocardial fibrosis. Comparisons between groups were made using ANOVA. Results:The insulin resistance index indicated no systemic insulin resistance in all groups. Echocardiography revealed that compared with the FLOX group, the FLOX-ISO group exhibited significant reductions in left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic volume(LVESV), and left ventricular end-diastolic volume(LVEDV), along with increases in heart weight-to-body weight(HW/BW), left ventricular end-systolic diameter(LVESD), and left ventricular end-diastolic diameter(LVEDD). Compared with the FLOX-ISO group, the CKO-ISO group showed significantly increased LVEF and decreased LVESV, LVEDV, LVESD, and LVEDD. Immunohistochemistry results demonstrated that myocardial TSHR knockout increased the expression of IRS-1 and GLUT-4. Additionally, RT-qPCR and Western blotting showed that ANP, BNP, and β-MHC expression levels were reduced, while IRS-1, IRβ, and GLUT-4 expression levels were elevated in TSHR CKO mice. Conclusion:Cardiomyocyte-specific TSHR knockout improves myocardial insulin resistance in mice with heart failure.
