P59: The protective effects of exogenous hydrogen sulfide against global cerebral ischemia/reperfusion injury in rats

Recent studies demonstrated the neuro-protective role of H2S during a moderate brain injury. In this study, we employed a rat cerebral I/R model with longer time global ischemia and investigated the effect of H2S on a much more severe cerebral injury, as well as 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 mmol/kg significantly decreased the apoplexy index, neurological symptom scoring, and brain infracted area as compared to the I/R group. 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 p47phox and gp91phox subunits of NADPH oxidase were also suppressed by NaHS treatment. 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 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 pro-apoptotic 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. 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.