Exogenous hydrogen sulfide protects against global cerebral ischemia/reperfusion injury via its anti-oxidative, anti-inflammatory and anti-apoptotic effects in rats

被引:138
作者
Yin, Jun [1 ]
Tu, Chao [1 ]
Zhao, Jie [2 ]
Ou, Danmin [3 ]
Chen, Guangwen [3 ]
Liu, Ying [3 ]
Xiao, Xianzhong [3 ]
机构
[1] Cent S Univ, Clin Med Year Program 8, Xiangya Sch Med, Changsha 410078, Hunan, Peoples R China
[2] Cent S Univ, Dept Neurosurg, Xiangya Sch Med, Changsha 410078, Hunan, Peoples R China
[3] Cent S Univ, Dept Pathophysiol, Xiangya Sch Med, Lab Shock, Changsha 410008, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
Hydrogen sulfide (H2S); Ischemia-reperfusion; Brain; Oxidative stress; Inflammation; Apoptosis; TUMOR-NECROSIS-FACTOR; ISCHEMIA-REPERFUSION INJURY; OXIDATIVE STRESS; NADPH OXIDASE; LIPID-PEROXIDATION; MOLECULAR-BIOLOGY; H2S PROTECTS; IN-VIVO; BRAIN; EXPRESSION;
D O I
10.1016/j.brainres.2012.10.046
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study was undertaken to study the effects of exogenous hydrogen sulfide (H2S) on global cerebral ischemia-reperfusion(I/R) and the underlying mechanisms. After a 24 h I/R, administration of NaHS, an exogenous donor for H2S, at the dose of 0.2 or 0.4 mu mol/kg significantly decreased the apoplexy index, neurological symptom scoring, and brain infarcted area as compared to the I/R group in a dose dependent manner. At the same time, NaHS-treated rats displayed significant reduction of MDA content, and striking increase of SOD activity in the brain tissues compared with I/R group. The up-regulated mRNA levels of p47(phox) and gp91(phox) subunits of NADPH oxidase were also suppressed by NaHS treatment. In this study, the pro-inflammatory markers TNF-alpha and MCP-1 in I/R group were markedly increased by 24 h I/R, which were significantly attenuated by NaHS in a dose-dependent manner. In contrast, the anti-inflammatory factor IL-10 was markedly induced by NaHS administration. In addition, the expression of the anti-apoptotic protein Bcl-2 was significantly decreased in I/R group compared with the sham-operated group. This reduction was significantly blunted in NaHS-treated group. On the contrary, the proapoptotic protein Bax content in brain tissues of I/R group was markedly elevated compared with sham-operated animals. And such an induction of Bax content was significantly ameliorated by NaHS. Taken together, our results suggest that hydrogen sulfide has potent protective effect against a severe cerebral injury induced by a global I/R possibly through the inhibition of oxidative stress, inflammation and apoptosis. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:188 / 196
页数:9
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