参附注射液抑制NLRP3炎症小体介导的小胶质细胞焦亡减轻老年大鼠术后认知功能障碍OA

Objective To investigate the effect of Shenfu Injection(SFI)on postoperative cognitive dysfunction(POCD)in aged rats.Methods An elderly rat model of postoperative cognitive dysfunction(POCD)was established by using isoflurane inhalation anesthesia combined with splenectomy.The rats were randomly divided into the sham operation group,the model group,and the treatment group,with 24 rats in each group.In the in vitro experiment,the cultured microglial cells were divided into the blank group,the li-popolysaccharide(LPS)group,and the LPS+SFI group.Behavioral assessment was performed using the Morris water maze(MWM),the expression of nuclear factor-κB(NF-κB),NOD-like receptor thermal protein domain associated protein 3(NLRP3),cysteinyl aspartate specific protease-1(Caspase-1),apoptotic speck-like protein(ASC),and GSDMD in the hippocampal tissue of the rats was detected by Western blot,the levels of IL-1,IL-6,high mobility group box 1(HMGB1),and tumor necrosis factor-α(TNF-α)in the rat serum were detected by ELISA,the degree and fluorescence intensity of inflammatory cell infiltration in the rat hippocam-pal tissue were observed by HE staining and immunofluorescence staining,and the morphological changes of pyroptosis of the microglial cells in the in vitro experiment were observed by scanning electron microscopy.Results Compared with the model group,the escape latency in the treatment group was shortened on the 3rd and 7th days after surgery(P<0.05)and significantly increased platform crossings(P<0.05).On the 3rd day after surgery,the expressions of GSDMD,NF-κB,NLRP3,ASC,and Caspase-1 decreased(P<0.05).On the 1st,3rd,and 7th days after surgery,the levels of HMGB1,IL-1,IL-6,and TNF-α decreased(P<0.05).The infiltration of inflammatory cells was significantly reduced,and the expression levels of NF-κB and GSDMD decreased.Compared with the LPS group,the pyroptosis of microglia in the LPS+SFI group was alleviated.Conclusion SFI may alleviate POCD by inhibiting the pyroptosis of microglia mediated by the NLRP3 inflammasome.