摘要OBJECTIVE:To explore the mechanism by which Tongqiao Yizhi granule(通窍益智颗粒,TQYZKL)intervenes pyroptosis to treat vascular dementia(VaD)in a rat model.METHODS:The rat model of VaD was established by two-vessel occlusion(2VO).The rats were randomly divided into Sham group,Model group,Nimodipine group,TQYZKL(6.2 g·kg-1·d-1),TQYZKL(12.4 g·kg-1·d-1),TQYZKL(24.8 g·kg-1·d-1).The Morris water maze(MWM)test was carried out to test the learning and memory function;Hematoxylin-eosin staining and transmission electron microscopy(TEM)to observe the pathological damage in the hippocampus;Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus.The expression levels of pyroptosis-related proteins,namely Golgi peripheral membrane protein p65(P65),nucleotide oligomerization domain-like receptors 3(NLRP3),caspase-1 and Gasdermin D(GSDMD),were detected using Western blotting and reverse transcription polymerase chain reaction.Moreover,the serum levels of interleukin-1 β(IL-1β)and interleukin-18(IL-18)were determined through the enzyme-linked immunosorbent assay.RESULTS:The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize,relieved the pathological damage in the hippocampus,restored neuronal morphology,and reduced the expression of pyroptosis-related proteins P65,NLRP3,caspase-1,GSDMD-N,IL-18 and IL-1β(P＜0.05).CONCLUSION:TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway,thus exerting a therapeutic effect on VaD in the rats.