基于NLRP3/Caspase1/GSDMD信号通路探讨对缺血性脑卒中后失眠大鼠的改善作用OA

Objective:To investigate the therapeutic effect of repetitive transcranial magnetic stimulation(rTMS)of different intensities on rats with ischemic stroke-induced insomnia based on the NLRP3/Caspase1/GSDMD signaling pathway.Methods:Rats were randomly separated into a sham surgery group,a model group,a high-frequency rTMS group,a low-frequency rTMS group,an estazolam group,and a low-frequency rTMS+DDC group using the random number table method,with 12 rats in each group.A model of ischemic stroke-in-duced insomnia was prepared by temporary middle cerebral artery occlusion surgery and intraperitoneal injec-tion of chlorpheniramine suspension.Rats were intervened with rTMS,positive drug escitalopram,and NLRP3 activator diethyldithiocarbamate(DDC)for 14 days,then,the sleep phase indicators of rats were detected,in-cluding sleep phase awakening(Wake),slow wave sleep phase one(SWS1),slow wave sleep phase two(SWS2),and rapid eye movement sleep phase(REMS).HE staining and TUNEL staining were used to detect pathological changes and neuronal apoptosis in rat brain tissue,respectively.ELISA was used to detect serum melatonin(MT),5-hydroxytryptamine(5-HT),norepinephrine(NA),dopamine(DA),and inflammatory factors in rats.In addition,immunofluorescence staining and Western blot were used to detect the protein ex-pression of NLRP3/Caspase1/GSDMD signaling pathway in rat brain tissue.Results:Compared with the sham surgery group,the model group showed a prominent decrease in SWS1,SWS2,REMS,serum MT and 5-HT levels(P<0.05),while a prominent increase in Wake,neuronal apoptosis index,serum NA,DA,IL-1β,IL-6 and IL-18 levels,brain tissue NLRP3,Caspase1 and GSDMD expression(P<0.05).Compared with the model group,the high-frequency rTMS group,low-frequency rTMS group,and estazolam group showed an increase in SWS1,SWS2,REMS,serum MT and 5-HT levels(P<0.05),while a decrease in Wake,neuronal apoptosis index,serum NA,DA,IL-1β,IL-6 and IL-18 levels,brain tissue NLRP3,Caspase1 and GSDMD expression(P<0.05).The low-frequency rTMS group and estazolam group showed a further increase in SWS1,SWS2,REMS,serum MT and 5-HT levels(P<0.05),while a further decrease in Wake,neuronal apoptosis index,se-rum NA,DA,IL-1β,IL-6 and IL-18 levels,brain tissue NLRP3,Caspase1 and GSDMD expression than the high-frequency rTMS group(P<0.05).Compared with the low-frequency rTMS group,the low-frequency rT-MS+DDC group showed a decrease in SWS1,SWS2,REMS,serum MT and 5-HT levels(P<0.05),while an increase in Wake,neuronal apoptosis index,serum NA,DA,IL-1β,IL-6 and IL-18 levels,brain tissue NL-RP3,Caspase1 and GSDMD expression(P<0.05).Conclusion:rTMS can improve insomnia symptoms in is-chemic stroke-induced insomnia rats by downregulating the protein expression of NLRP3/Caspase1/GSDMD signaling pathway.