Effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy
10.3760/cma.j.issn.0254-9026.2023.09.014
- VernacularTitle:钠-葡萄糖协同转运蛋白2抑制剂达格列净对糖尿病心肌病小鼠心肌重构的影响
- Author:
Xiaoxing LI
1
;
Jiajun ZHANG
;
Xinhui FAN
;
Xintian SONG
;
Feng XU
;
Xiaoping JI
;
Yuguo CHEN
;
Chuanbao LI
Author Information
1. 山东大学齐鲁医院老年医学科，济南 250012
- Keywords:
Sodium-glucose cotransporter 2 inhibitor;
Diabetic mellitus;
Cardiomyopathies;
Ventricular remodeling
- From:
Chinese Journal of Geriatrics
2023;42(9):1099-1104
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods:Between January and December 2021, 60 6-week-old male C57BL/6J mice were chosen for the study, 40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice, of whom, 14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound, the degree of myocardial fibrosis was evaluated by histology and electron microscopy, the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays, apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL), and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results:At the end of the experiments, the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group, but the difference was not statistically significant, while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)% vs.(45.8±4.80)%, t=-5.24, P<0.05].Compared with the non-intervention group, the intervention group had alleviated myocardial hypertrophy, less myocardial disarray, and reduced collagen volume fraction[(18.4±1.9)% vs.(31.8±3.7)%, t=-12.0, P<0.05].Furthermore, the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6: (82.19±10.90)ng/L vs.(291.02±31.02)ng/L, t=23.8, P<0.05; tumor necrosis factor-α: (70.45±12.13)ng/L vs.(201.31±27.10)ng/L( t=16.5), P<0.05; perforin 3: (13.05±2.04)μg/L vs.(42.40±1.26)μg/L( t=45.8), P<0.05; the index of myocardial apoptosis: 1.736±0.247 vs.0.864±0.129, t=11.7, P<0.05].The level of myocardial oxidative stress in the non-intervention group was higher than in the intervention group(2.655±0.252 vs.1.274±0.298, t=-13.3, P<0.05). Conclusions:Dapagliflozin can reduce myocardial hypertrophy and inhibit myocardial fibrosis through mitigating myocardial oxidative stress and inflammatory response, thus suppressing myocardial remodeling and ultimately protecting cardiac function in diabetic cardiomyopathy mice.
