Hydrogen sulfide attenuates cardiac dysfunction in a rat model of heart failure: a mechanism through cardiac mitochondrial protection

被引:85
作者
Wang, Xianli
Wang, Qian
Guo, Wei
Zhu, Yi Zhun [1 ]
机构
[1] Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China
关键词
apoptosis; heart failure; heart function; hydrogen sulfide; mitochondria; myocardial infarction; VIRAL GENE-TRANSFER; MYOCARDIAL-ISCHEMIA; MYOCYTE APOPTOSIS; ENDOGENOUS PRODUCTION; GASEOUS TRANSMITTER; DEATH; H2S; CARDIOMYOPATHY; NEUROMODULATOR; INFLAMMATION;
D O I
10.1042/BSR20100003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
HF (heart failure) after MI (myocardial infarction) is a major cause of morbidity and mortality worldwide. Recent studies have shown that hydrogen sulfide (H2S) has cardioprotective effects. Hence, we aimed to elucidate the potential effects of H2S on HF after MI in rats. The HF model after MI was made by ligating the left anterior descending coronary artery. HF groups and sham-operated groups of rats were treated with vehicle, sodium hydrosulfide (NaHS) or PAG (propagylglycine). Equal volumes of saline, 3.136 mg . kg(-1) day(-1) NaHS or 37.5 mg . kg(-1) . day(-1) PAG, were intraperitoneally injected into rats for 6 weeks after operation. Survival, lung-to-body weight ratio and left ventricular haemodynamic parameters were measured. The protein and gene expression of Bcl-2, Bax, caspase 3 and cytochrome c were analysed by Western blotting and RT-PCR (reverse transcription-PCR). TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) and EM (electron microscopy) were used to examine apoptosis of heart tissues. NaHS was found to improve the survival and lower the lung-to-body weight ratio. It increased the LVSP (left ventricular systolic pressure) and the maximum rate of pressure and decreased LVEDP (left ventricular end-diastolic pressure). Furthermore, NaHS promoted Bcl-2 protein and mRNA expression and demoted Bax, caspase 3 protein and mRNA expression in HF rats. We also showed that NaHS decreased the leakage of cytochrome c protein from the mitochondria to the cytoplasm. Histological observation by TUNEL and EM proved that NaHS inhibited cardiac apoptosis in HF hearts and improved mitochondrial derangements, but that PAG aggravated those indices. Hence, H2S has protective effects in HF rats.
引用
收藏
页码:87 / 98
页数:12
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