Effect of the mitochondrial H2S donor AP39 on myocardial fibrosis in rats with myo-cardial infarction and its relationship to mitochondrial dynamics
10.20039/j.cnki.1007-3949.2024.06.003
- VernacularTitle:线粒体H2S供体AP39对心肌梗死大鼠心肌纤维化的影响及其与线粒体动力学的关系
- Author:
Ting YANG
1
,
2
;
Qi LAI
;
Jun YANG
;
Chun CHU
Author Information
1. 南华大学药学院,湖南省衡阳市 421001
2. 南华大学衡阳医学院附属第二医院药剂科,湖南省衡阳市 421001
- Keywords:
hydrogen sulfide;
AP39;
mitochondrial fusion;
mitochondrial division;
myocardial infarction;
myocardial fibrosis
- From:
Chinese Journal of Arteriosclerosis
2024;32(6):473-480
- CountryChina
- Language:Chinese
-
Abstract:
Aim Previous studies have indicated that H2S can attenuate myocardial fibrosis.However,it is unclear whether mitochondria-targeted H2S can attenuate myocardial fibrosis after myocardial infarction and whether its mechanism is associated with the regulation of mitochondrial fusion and fission.To investigate this relationship,this study was conducted.Methods Isoproterenol(ISO,50 mg/(kg·d))was injected intraperitoneally to induce myocardial infarction in SD rats.Electrocardiograms were performed on each group of rats,and the rats were treated with AP39(36 μg/(kg·d),intraperitoneal)for 4 weeks.Masson's staining was used to assess the extent of myocardial fibrosis.Western blot was used to measure the expression of relevant proteins.In vitro experiments were performed to induce hy-poxic injury in H9c2 cardiomyocytes with CoCl2(800 μmol/L),H9c2 cells were treated with AP39(100 nmol/L),and the endogenous hydrogen sulfide synthase cystathionine-γ-lyase(CSE)was inhibited using DL-propargylglycine(PAG,2 mmol/L),and fluorescence probe was used to measure the level of reactive oxygen species(ROS)in myocardial cells.Results Myocardial fibrosis was evident in infarcted rat hearts,with a significant accumulation of collagen fibers.Addi-tionally,the expression of CSE and mitofusin 2(MFN2)proteins was downregulated,while dynamin-related protein 1(DRP1)protein expression was increased.Intervention with AP39 significantly improved the above changes,and the ad-dition of CSE inhibitor PAG reversed the effects of AP39.In in vitro experiments,when H9c2 myocardial cells were sub-jected to hypoxic injury induced by CoCl2,intracellular ROS levels increased,MFN2 expression was downregulated,and DRP1 expression was upregulated.AP39 upregulated MFN2 protein expression,inhibited DRP1 protein expression,and reduced ROS levels in myocardial cells.The addition of PAG reversed these changes.Conclusion The mitochon-dria-targeted H2S donor,AP39,can improve myocardial fibrosis in rats with myocardial infarction and promote mitochon-drial fusion and inhibit excessive mitochondrial division.
