Hydrogen sulfide inhibits apoptosis of cardiomyocytes and ameliorates myocardial fibrosis in rats after myocardial infarction through downregulating Yes-related protein 1 and a transcriptional co-activator with a PDZ-binding motif
10.3760/cma.j.issn.0254-9026.2023.08.014
- VernacularTitle:硫化氢下调Yes相关蛋白1和含PDZ结合基序的转录共激活因子抑制大鼠心肌梗死心肌细胞凋亡及改善心肌纤维化的机制研究
- Author:
Liuyang WANG
1
;
Aimin ZHANG
;
Junxiong ZHAO
;
Liangui NIE
;
Shengquan LIU
;
Ting XIAO
;
Jun YANG
Author Information
1. 南华大学第一附属医院心内科，衡阳 421001
- Keywords:
Hydrogen sulfide;
Myocardial infarction;
Fibrosis;
Apoptosis;
YAP1/TAZ signaling pathway
- From:
Chinese Journal of Geriatrics
2023;42(8):964-969
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of exogenous hydrogen sulfide on myocardial fibrosis and apoptosis in rats after myocardial infarction and the underlying mechanisms.Methods:Forty-three Sprague Dawley(SD)rats were divided into 4 groups according to the random number table method: a control group(n=12), a myocardial infarction group(MI group, n=13), an hydrogen sulfide(H 2S)group(n=6)and an MI+ H 2S group(n=12). The rat model of acute myocardial infarction was established by intraperitoneal injections of isoproterenol(50 mg/kg, once a day, for 2 days). Electrocardiogram and troponin changes were recorded 48 h after the last drug administration to determine whether the rat model was successfully constructed.After successful establishment of the model, rats in the MI group and the MI+ H 2S group were intraperitoneally injected with sodium hydrosulfide(56 μmol/kg, once a day, for 6 weeks).6 weeks later, echocardiogram and Masson's trichrome staining were performed to assess changes in cardiac function and collagen volume fraction in each group.Terminal deoxynucleotidyl transferase(TdT)dUTP nick end labeling(TUNEL)was used to detect the myocardial apoptosis rate in each group, and Western-blot was used to detect protein expression of Yes-related protein 1(YAP1), WW domain containing transcriptional regulator1(TAZ), mammalian Ste20-like kinase 2(MST2), Bcl-2-associated X protein(Bax), cysteine protease 3(caspase-3), the ratio of matrix metalloproteinase 3(MMP3)/matrix metalloproteinase inhibitor 2(TIMP2), and B-cell lymphoma factor(Bcl-2). Results:Compared with the control group, myocardial collagen volume fraction was increased( P<0.05), the myocardial cell apoptosis rate was increased( P<0.05), and myocardial YAP1, TAZ, MST2, Bax, caspase-3 protein expression and MMP3/TIMP2 ratio were increased in the MI group(all P<0.05), while the expression of Bcl-2 protein was decreased( P<0.05). Compared with the MI group, collagen volume fraction and the cardiomyocyte apoptosis rate were significantly decreased in the MI+ H 2S group( P<0.05). Also, protein expression of YAP1(2.406±0.024 vs.2.830±0.063), TAZ(0.964±0.090 vs.1.329±0.018), MST2(0.780±0.082 vs.1.788±0.097), Bax(1.500±0.008 vs.0.613±0.003)and caspase-3(0.620±0.024 vs.0.780±0.012)and the MMP3/TIMP2 ratio were decreased(all P<0.05), while protein expression of Bcl-2 was increased( P<0.05)in myocardial tissue. Conclusions:H 2S can mitigate myocardial fibrosis after myocardial infarction, through inhibiting the activation of the YAP1/TAZ signaling pathway, thus reducing apoptosis of cardiomyocytes.
