Objective To explore the effect and mechanism of sodium hydrosulfide(NaHS)on cerebral cortical injury in rats with cerebral ischemia-reperfusion.Methods A total of 80 male SD rats were divided into a sham operation group,an NaHS group,an ischemia-reperfusion group,and an ischemia-reperfusion+NaHS group using a random number table method,with 20 rats in each group.The rats in the ischemia-reperfusion group and ischemia-reperfusion+NaHS group were used to prepare ischemia-reperfusion models.The rats in the ischemia-reperfusion+NaHS group were given 50 μmol·kg-1 NaHS intraperitoneally after cerebral ischemia,while the rats in the ischemia-reperfusion group were given an equal volume of physiological saline intraperitoneally after cerebral ischemia.The rats in the sham operation group and NaHS group only had vessels isolated but not occluded with threads.The rats in the NaHS group were given 50 μmol·kg-1 NaHS intraperitoneally after vascular detachment,while the rats in the sham operation group were given an equal volume of physiological saline intraperitoneally after vascular detachment.Twenty-four hours after modeling,the neurological deficits of rats in the four groups were evaluated by using the modified neurological severity score(mNSS),the cerebral infarction of rats in the four groups was observed aftertriphenyltetrazolium chloride staining,the levels of pro-inflammatory cytokines interleukin-1β(IL-1β)and interleukin-18(IL-18)in theischemiccerebralcortical tissues of rats in the four groups were detected by using enzyme-linked immunosorbent assay,the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in the ischemic cerebral cortical tissues of rats in the four groups was detected by using Western blot,and the activity of microglia in the ischemic cerebral cortical tissues of rats in the four groups was detected by using immunofluorescence.Results The brain tissues of rats in the sham operation group and the NaHS group showed uniform orange red color,while the rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group had pale infarcted areas in the ischemic cerebral cortex and striatum.The cerebral infarction area of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly larger than that in the sham operation group and the NaHS group,while the cerebral infarction area of rats in the ischemia-reperfusion+NaHS group was significantly smaller than that in the ischemia-reperfusion group(P＜0.05).The mNSS scores of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly higher than those in the sham operation group and the NaHS group,while the mNSS score of rats in the ischemia-reperfusion+NaHS group was significantly lower than that in the ischemia-reperfusion group(P＜0.05).The relative expression levels of NLRP3 protein in the ischemic cerebral cortex of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly higher than those in the sham operation group and the NaHS group,while the relative expression level of NLRP3 protein in the ischemic cerebral cortex of rats in the ischemia-reperfusion+NaHS group was significantly lower than that in the ischemia-reperfusion group(P＜0.05).The levels of IL-1β and IL-18 in the ischemic cerebral cortex of rats in the ischemia-reperfusion group and the ischemia-reperfusion+NaHS group were significantly higher than those in the sham operation group and the NaHS group,while the levels of IL-1β and IL-18 in the ischemic cerebral cortex of rats in the ischemia-reperfusion+NaHS group were significantly lower than those in the ischemia-reperfusion group(P＜0.05).The rats in both sham operation group and NaHS group showed normal morphology of microglia in the ischemic cerebral cortical area.Compared with the sham operation group and the NaHS group,the rats in the ischemia-reperfusion group showed a significant reduction in the protrusion of microglia in the ischemic cerebral cortical area and a significant increase in the brightness of microglial cell bodies,and the cells appeared as clumps,losing their normal morphology,with a higher proportion of activated microglia.Compared with the ischemia-reperfusion group,the rats in the ischemia-reperfusion+NaHS group showed an increase in the number of microglial processes in the ischemic cerebral cortex,with fewer activated microglia and significantly improved morphology.The total numbers of microglia in the ischemic cerebral cortex of rats in the ischemia-reperfusion group and theischemia-reperfusion+NaHS group were significantly lower than those in the sham operation group and the NaHS group,while the total number of microglia in the ischemic cerebral cortex of rats in the ischemia-reperfusion+NaHS group was significantly higher than that in the ischemia-reperfusion group(P＜0.05).Conclusion NaHS can significantly improve brain injury in ischemia-reperfusion rats by inhibiting the inflammatory response and microglial activation induced by NLRP3 and reducing the levels of pro-inflammatory cytokines IL-1β and IL-18.
sodium hydrosulfidecerebral ischemia-reperfusionmicroglial activationcortical injuryinflammationnucleotide binding oligomerization domain like receptor protein 3
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