Abstract 2463: Hydrogen Sulifde, A Novel Gasotransmitter, And Ischemic Stroke: Its Protective Role In Cerebral Ischemic - Reperfusion Injury Model

Abstract

Backgoround: Hydrogen sulfide (H2S) has recently been highligted as the third gasotransmitter following its two counterparts, nitric oxide and carbon monoxide. Several lines of evidence have demonstrated that H2S is a potent vasodilator and has a protective role in ischeic-reperfusion injury of several organs, including heart, liver and kidney. In the present study, we examined the protective effect of H2S in rodent cerebral ischemia-reperfusion injury model. Methods: Ischemia-reperfusion injury model wsa induced by intraluminal middle cerebral artery occlusion (MCAo) for 120 min followed by reperfusion in Male Sprague Dawley rats. Sodium hydrosulfide (NaHS, 1mg/kg and 5mg/kg), the donor of H2S, and normal saline (1mL) was infused via tail vein, immediately after reperfusion. To confirm the protective effect of H2S, we used propargylglycine (PAG)(50mg/kg, intraperitoneal for 7 days befor MCAo). We used Nissl stain to measure infarct sizes, ELISA to determine the levels of IL-1b, IL-6 and TNF-a in the brain, and Western blot to assess the expression of ERK 1/2, STAT 3, phosphorylated STAT3, and Nrf 2. In addition, GSH/GSSG ratio and lipid peroxidase were measured to assess the levels of oxidative stress. Results: Injection of H2S significantly reduced infarct size (5mg/kg: 43 ± 10%; 1mg/kg: 48 ± 12% vs. Control: 58 ± 11%, p < 0.05, n= 9-11). Furthermore, intraperitoneal injection of PAG worsened the infarct size (n=5, p<0.01). Administration of NaHS (5mg/Kg) significantly increased STAT3 phosphorylation at 24 hour after ischemia (n=4, p<0.01). Furthermore, Nrf2, an important molecular in anti-oxidative response, expression signicantly increased in experiment group at 24 and 48 horus after ischemic compared with control (n=4, p<0.01). ELISA showed that the levels of IL-6 increased in experiement gorup (2.5 ± 0.5 ng/mL, n = 4) at 24 and 48 hours after ischemia compared with control gorup (1.9 ± 0.2 ng/mL, n = 4). The levels of IL-1b increased in H2S gorup (0.7 ± 0.1 ng/mL, n = 4) at 48 hours after ischemia but not at 24 hours compred with control (0.4 ± 0.1mg/mL, n = 4). However, TNF-a levels were not different. The levels of GSH/GSSG ratio and lipid perixidase were significantly lower in H2S treated gorup compared with control (p < 0.05, n = 4). Conclusion: In the present study, we showed that administration of NaHS, the donor of H2S, protects brain from ischemia-reperfusion injury. This effect may be driven from anti-oxidative and anti-inflammatory effects of H2S.