Mechanism of Jianpi Huayu Jiedu Formula on alleviating gastric precancerous lesion via regulating PKA/NLRP3 signaling pathway
Objective:To explore the mechanism of Jianpi Huayu Jiedu Formula(JPHYJD)in alleviating gastric precancerous lesion(GPL).Methods:Animal experiment 1:A total of 60 mice were randomly divided into control group,model group,JPHYJD high and low dose groups,and Vitacoenzyme group.After treatment,HE staining was used to observe the pathological changes of gastric mucosa,and immunofluorescence staining was used to observe the expression of NLRP3 and GSDMD;Animal experiment 2:A total of 60 mice were randomly divided into control group,model group,H89 group,model+H89 group,JPHYJD group,and model+H89+JPHYJD group.Western Blot was used to detect the expression of GSDMD-N,Caspase-1,and IL-1 β.Cell experiment 1:THP-1 cells were divided into control group,model group and JPHYJD group.After modeling with LPS+ATP,the JPHYJD group was treated with drug containing serum.Cell experiment 2:THP-1 cells were divided into groups the same as animal experiment 2.After treatment with H89 and drug containing serum,the expression of pyroptosis related molecules and PI staining were detected.Results:In vivo,compared with the control group,the model group showed GPL lesions and increased expression of NLRP3 and GSDMD(P＜0.01).JPHYJD could improve gastric mucosal lesions and inhibit the expression of NLRP3 and GSDMD(P＜0.01,P＜0.05).Compared with the control group,the model group showed increased expression of GSDMD-N,Caspase-1,and IL-1 β(P＜0.01),and JPHYJD could inhibit their expression(P＜0.0l).The expression level of the model+H89+JPHYJD group was higher than that of the JPHYJD group(P＜0.05).In vitro,compared with the control group,the model group showed increased expression of NLRP3,GSDMD-N,Caspase-1,IL-1 β protein and mRNA,as well as elevated levels of pyroptosis(P＜0.01,P＜0.05).JPHYJD significantly inhibited the expression of these molecules and reduced cell pyroptosis(P＜0.01).Compared with the control group,the model group showed a decrease in PKA,an increase in NLRP3,GSDMD-N,IL-1 β,and an increase in pyroptosis levels(P＜0.01).While JPHYJD upregulated PKA,inhibited NLRP3,GSDMD-N,IL-1 β,and reduced cell pyroptosis(P＜0.0l,P＜0.05).Compared with the JPHYJD group,the model+H89+JPHYJD group showed a decrease in PKA,an increase in NLRP3,GSDMD-N,IL-1 β expression,and an increase in pyroptosis(P＜0.01).Conclusion:JPHYJD alleviates GPL via regulating PKA/NLRP3 pathway.
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