Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through cardiac mitochondrial protection
Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through cardiac mitochondrial protection
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硫氢化钠通过保护心肌线粒体减轻高同型半胱氨酸血症大鼠心肌损伤
DOI：
10.1007/s11010-014-2245-6
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Liu YH
中科院分区：
文献类型：
--
作者：
Wu J;Song M;Zhong X;Liu YH
硫化氢（H2S）在大鼠心肌损伤中起重要作用。然而，H2S在高同型半胱氨酸血症（HHcy）引起的心功能不全中的作用以及潜在的机制知之甚少。在这项研究中，我们研究了硫氢化钠（NaHS，H2S供体）是否影响蛋氨酸诱导的HHcy大鼠心肌损伤在完整的大鼠心脏和原代新生大鼠心肌细胞。HHcy + NaHS治疗组采用蛋氨酸（2.0g/kg）诱导HHcy大鼠模型，每日给予80 μmol/L NaHS。分别于4、8、12周末用透射电镜和超声心动图系统观察心脏超微结构的改变和功能。检测心肌细胞凋亡率、线粒体膜电位和活性氧（ROS）的产生。Western blotting检测CSE、Bax和Bcl-2、caspase-3、磷酸化内皮型一氧化氮合酶（PENOS）、线粒体NOX 4和细胞色素c的表达。结果表明，高同型半胱氨酸可引起大鼠心功能不全，心肌超微结构改变，心肌细胞凋亡率增加。HHcy组原代乳鼠心肌细胞ROS生成明显增加，CSE表达减少。NaHS处理可明显改善HHcy组大鼠心脏功能和超微结构的改变，降低HHcy组原代乳鼠心肌细胞ROS水平。此外，NaHS还可下调线粒体NOX 4、caspase-3和Bax的表达，抑制线粒体细胞色素c的释放。结论：H2S通过保护心肌线粒体参与减轻HHcy心肌损伤。
Hydrogen sulfide (H2S) plays an important role during rat myocardial injury. However, little is known about the role of H2S in hyperhomocysteinemia (HHcy)-induced cardiac dysfunction as well as the underlying mechanisms. In this study, we investigated whether sodium hydrosulfide (NaHS, a H2S donor) influences methionine-induced HHcy rat myocardial injury in intact rat hearts and primary neonatal rat cardiomyocytes. HHcy rats were induced by methionine (2.0 g/kg) and the daily administration of 80 μmol/L NaHS in the HHcy + NaHS treatment group. At the end of 4, 8, and 12 weeks, the ultrastructural alterations and functions of the hearts were observed using transmission electron microscopy and echocardiography system. The percentage of apoptotic cardiomyocytes, the mitochondrial membrane potential, and the production of reactive oxygen species (ROS) were measured. The expressions of cystathionine-γ-lyase (CSE), Bax and Bcl-2, caspase-3, phospho-endothelial nitric oxide synthase and the mitochondrial NOX4 and cytochrome c were analyzed by Western blotting. The results showed the cardiac dysfunction, the ultrastructural changes, and the apoptotic rate increase in the HHcy rat hearts. In the primary neonatal rat cardiomyocytes of HHcy group, ROS production was increased markedly, whereas the expression of CSE was decreased. However, treatment with NaHS significantly improved the HHcy rat hearts function, the ultrastructural changes, and decreased the levels of ROS in the primary neonatal rat cardiomyocytes administrated with HHcy group. Furthermore, NaHS down-regulated the expression of mitochondrial NOX4 and caspase-3 and Bax and inhibited the release of cytochrome c from mitochondria. In conclusion, H2S is involved in the attenuation of HHcy myocardial injury through the protection of cardiac mitochondria.
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DOI：
10.1126/science.1162667
发表时间：
2008-10-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yang G;Wu L;Jiang B;Yang W;Qi J;Cao K;Meng Q;Mustafa AK;Mu W;Zhang S;Snyder SH;Wang R
通讯作者：
Wang R
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.3
作者：
Xin Zhong;Leihong Wang;Yuwen Wang;Shiyun Dong;Xiaoning Leng;J. Jia;Yajun Zhao;Hulun Li;
通讯作者：
Xin Zhong;Leihong Wang;Yuwen Wang;Shiyun Dong;Xiaoning Leng;J. Jia;Yajun Zhao;Hulun Li;
DOI：
10.1073/pnas.96.14.8144
发表时间：
1999-07-06
影响因子：
11.1
作者：
Narula, J;Pandey, P;Kharbanda, S
通讯作者：
Kharbanda, S
影响因子：
2
作者：
Y. Zhuo;Pei-fang Chen;A. Zhang;Han Zhong;Chang-qing Chen;Yi-Zhun Zhu
通讯作者：
Y. Zhuo;Pei-fang Chen;A. Zhang;Han Zhong;Chang-qing Chen;Yi-Zhun Zhu