大豆异黄酮通过抑制NLRP3炎症小体介导的神经元焦亡改善脑缺血再灌注损伤OA

Objective:To explore the neuroprotective effect and mechanism of soy isoflavones(SI)on cerebral ischemia-reperfusion injury(CIRI)by inhibiting NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome-mediated neuronal pyroptosis.Methods:Sixty healthy Sprague-Dawley(SD)rats were randomly divided into sham group,model group,SI group and SI+Nigericin group.Rats in the SI group were pre-treated with intragastric administration of SI(120 mg/kg)once daily for 21 consecutive days.The middle cerebra-lartery occlusion(MCAO)rat model was established by the suture-occluded method,and reperfusion was in-duced by withdrawing the suture after 2 hours of ischemia;the sham group only underwent vascular separation without suture insertion.Five minutes before reperfusion,rats in the SI+Nigericin group were injected with Nige-ricin(1 mg/kg)via the tail vein.Twenty-four hours after reperfusion,the severity of brain injury was assessed by neurological deficit score,brain water content(dry-wet weight method),2,3,5-triphenyltetrazolium chloride(TTC)staining,and hematoxylin-eosin(HE)staining.The expression of pyroptosis-related proteins was mea-sured by immunofluorescence staining and western blotting.The serum levels of interleukin(IL)-1β,IL-18 and the activity of lactate dehydrogenase(LDH)were measured by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the model group,the SI group exhibited significantly reduced neurological deficit scores,brain water content,cerebral infarct volume(P＜0.001),as well as obviously alleviated cortical patho-logical injury.In the SI group,the protein expression levels of NLRP3,Gasdermin D(GSDMD),GSDMD N-terminal domain(GSDMD-N),caspase-1,cleaved caspase-1,IL-18,IL-1β and IL-1β p17 were downregulated;se-rum IL-1β and IL-18 contents as well as LDH activity were reduced(all P＜0.05),and the fluorescence signals of NLRP3 and GSDMD-N in brain tissues were obviously weakened.Nigericin could partially reverse the above protective effects of SI(P＜0.05).Conclusion:SI reduces neuronal pyroptosis by inhibiting NLRP3 inflamma-some activation,thereby effectively alleviating CIRI and exerting neuroprotective effects.