Exogenous hydrogen sulfide attenuates diabetic myocardial injury through cardiac mitochondrial protection
Exogenous hydrogen sulfide attenuates diabetic myocardial injury through cardiac mitochondrial protection
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DOI：
10.1007/s11010-012-1435-3
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发表时间：
2012-09
影响因子：
4.3
通讯作者：
Xin Zhong;Leihong Wang;Yuwen Wang;Shiyun Dong;Xiaoning Leng;J. Jia;Yajun Zhao;Hulun Li;
中科院分区：
文献类型：
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作者：
Xin Zhong;Leihong Wang;Yuwen Wang;Shiyun Dong;Xiaoning Leng;J. Jia;Yajun Zhao;Hulun Li;
在这项研究中，我们研究了外源性H2S（硫化氢）如何通过完整大鼠心脏和原代新生大鼠心肌细胞的心脏线粒体保护和一氧化氮（NO）合成来影响链脲佐菌素（STZ）诱导的糖尿病心肌损伤。糖尿病+ NaHS治疗组通过STZ（50 mg/kg）和每日给予100 μM NaHS（硫氢化钠，H2S供体）诱导糖尿病。分别于术后4、8、12周末用透射电镜和超声心动图观察心脏形态学改变和功能变化。检测心肌细胞凋亡率、线粒体膜电位、活性氧（ROS）产生量和一氧化氮（NO）含量。Western blotting检测胱硫醚-γ-裂解酶（CSE）、caspase-3和caspase-9、线粒体NOX 4和细胞色素c的表达。结果表明，糖尿病大鼠心脏功能受损，形态学改变，细胞凋亡率增加。高糖组原代乳鼠心肌细胞ROS生成明显增加，CSE表达和NO水平降低。NaHS可明显逆转高糖诱导的糖尿病大鼠心脏功能和形态学改变，降低高糖诱导的原代乳鼠心肌细胞ROS和NO水平。NaHS还可下调原代乳鼠心肌细胞线粒体NOX 4、caspase-3和caspase-9的表达，抑制线粒体细胞色素的释放。总之，H2S通过保护心肌线粒体参与减轻糖尿病心肌损伤。
In the study, we investigated how exogenous H2S (hydrogen sulfide) influenced streptozotocin (STZ)-induced diabetic myocardial injury through cardiac mitochondrial protection and nitric oxide (NO) synthesis in intact rat hearts and primary neonatal rat cardiomyocytes. Diabetes was induced by STZ (50 mg/kg) and the daily administration of 100 μM NaHS (sodium hydrosulfide, an H2S donor) in the diabetes + NaHS treatment group. At the end of 4, 8, and 12 weeks, the morphological alterations and functions of the hearts were observed using transmission electron microscopy and echocardiography system. The percentage of apoptotic cardiomyocytes, the mitochondrial membrane potential, the production of reactive oxygen species (ROS) and the level of NO were measured. The expressions of cystathionine-γ-lyase (CSE), caspase-3 and -9, the mitochondrial NOX4 and cytochromecwere analyzed by western blotting. The results showed the cardiac function injured, morphological changes and the apoptotic rate increased in the diabetic rat hearts. In the primary neonatal rat cardiomyocytes of high glucose group, ROS production was increased markedly, whereas the expression of CSE and the level of NO was decreased. However, treatment with NaHS significantly reversed the diabetic rat hearts function, the morphological changes and decreased the levels of ROS and NO in the primary neonatal rat cardiomyocytes administrated with high glucose group. Furthermore, NaHS down-regulated the expression of mitochondrial NOX4 and caspase-3 and -9 and inhibited the release of cytochromecfrom mitochondria in the primary neonatal rat cardiomyocytes. In conclusion, H2S is involved in the attenuation of diabetic myocardial injury through the protection of cardiac mitochondria.