寿胎丸抑制NLRP3介导的滋养细胞焦亡改善母胎界面炎症反应的研究OA

Objective To investigate the therapeutic effect of Shoutai Pill(寿胎丸,STP)on recurrent spontaneous abortion(RSA)and its underlying mechanism,focusing on the NOD-like receptor protein 3(NLRP3)inflammasome and trophoblast pyroptosis.Meth-ods The classic CBA/J×DBA/2 mating combination served as the RSA model,while CBA/J×BALB/c mating served as the normal preg-nancy control.RSA model mice were randomly divided into four groups(n=10 per group):model,dydrogesterone,low-dose STP,and high-dose STP.Normal pregnant mice comprised the control group.All treatments were administered for 14 days.Embryo resorption rates were calculated.Placental histopathology and inflammation were evaluated by hematoxylin-eosin(HE)staining.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of NLRP3,Caspase-1,gasdermin D(GSDMD),IL-1β,and IL-18 in placental tissue were analyzed by Western blot(WB).The expres-sion of NLRP3 and Caspase-1 was localized by immunohistochemistry(IHC).Co-localization of NLRP3 in trophoblasts was assessed by immunofluorescence(IF).Results Compared with the control group,the model group exhibited a significantly higher embryo resorption rate(P<0.01),elevated serum levels of IL-1β and IL-18(P<0.01),increased placental inflammation,upregulated protein expression of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18(P<0.01),and enhanced co-expression of NLRP3 in trophoblasts(P<0.01).Compared with the model group,both the dydrogesterone and high-dose STP groups showed significantly reduced embryo resorption rates(P<0.01),decreased serum IL-1β and IL-18 levels(P<0.01),attenuated placental inflammation,downregulated expression of the aforementioned proteins(P<0.01),and diminished NLRP3 co-expression in trophoblasts(P<0.01).Conclusion STP attenuates inflammation at the maternal-fetal interface and improves pregnancy outcomes in RSA model mice,potentially by inhibiting NLRP3 inflammasome-mediated trophoblast pyroptosis.