Exogenous hydrogen sulfide attenuates brain edema and injury of focal cerebral ischemia-reperfusion in rats by inhibiting the expressions of occludin and zonula occludens-1 protein / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effects of exogenous hydrogen sulfide on brain edema and injury and their mechanisms. Methods Sixty male SD rats were randomly divided into a sham operation group, an ischemia-reperfusion group, a 30 ppm hydrogen sulfide group, and a 60 ppm hydrogen sulfide group (n =15 in each group; 1 ppm =1 mg/L). A model of focal cerebral ischemia for 2 h and reperfusion for 24 h was induced by middle cerebral artery occlusion. The neurological scores were observed after 24 h cerebral ischemia-reperfusion. The cerebral infarction volume, the degree of brain edema, and the changes of blood-brain barrier permeability were measured. Western blotting was used to detect the expressions of occludin and zonula occludens-1 protein (ZO-1) in ischemic penumbra. Results Compared with the ischemia-reperfusion group, the neurological function scores in the 30 ppm and 60 ppm hydrogen sulfide group significantly increased in a dose-dependent manner (al P brain edema aleviated (al P < 0.05). The content of Evans blue in the ischemic brain tissue in the ischemia-reperfusion group increased significantly compare with the sham operation group (0.74 ±0.14 μg/100 mg vs. 0.19 ±0.06 μg/100 mg; P <0.05). The content of Evans blue in the brain tissue in the 30 ppm hydrogen sulfide group (0.55 ±0.10 μg/100 mg ) and the 60 ppm hydrogen sulfide group (0.35 ±0.08 μg/100 mg ) decreased significantly compared with the ischemia-reperfusion group (al P < 0.05), among them the 60 ppm hydrogen sulfide group was significantly lower than the 30 ppm hydrogen sulfide group (P <0.05). Western blot analysis showed that expression levels of occludin in penumbra (0.621% ±0.101% vs.0.787% ±0.087% vs.0.453% ± 0.127%; P <0.05) and ZO-1 (0.602% ±0.118% vs.0.778% ±0.805% vs.0.426% ±0.146; P <0.05) in the 30 ppm and 60 ppm hydrogen sulfide groups increased significantly compared with the ischemia-reperfusion group, among them, the expression levels of occludin and ZO-1 in the 60 ppm hydrogen sulfide group were significantly higher than those in the 30 ppm hydrogen sulfide group (al P < 0.05). Conclusions Inhalation of exogenous hydrogen sulfide can significantly attenuate brain edema after ischemia-reperfusion in a dose dependent manner, reduce infarct volume, and improve neurological function.Their mechanisms may be associated with inhibiting the downregulated expressions of occludin and ZO-1 and maintaining the integrity of the blood-brain barrier.