基于网络药理学和动物实验探讨生腺布液汤治疗干燥综合征的作用机制OA

Objective To explore the mechanism of Shengxian Buye Decoction in the treatment of Sjögren's syndrome(SS)using network pharmacology;To conduct animal experiments for validation.Methods TCMSP,HERB and TCMID databases were used to retrieve and screen the active components and corresponding targets of Shengxian Buye Decoction.The core components were obtained through the drug-component-target network,and the SS disease targets were retrieved from GeneCards,OMIM,TTD,PharmGKB,and DrugBank databases.The protein-protein interaction network was constructed and the core targets were screened.The intersection targets were enriched by GO and KEGG pathways.A total of 24 SS model NOD mice were randomly divided into the Chinese materia medica group,Western medicine group,and model group,with 8 mice in each group;another 8 BALB/c mice were selected as the normal group.The mice in each group were intragastrically administered with Shengxian Buye Decoction(9.88 g/kg),hydroxychloroquine sulfate solution(0.052 g/kg),and an equal volume of distilled water,respectively,for 8 consecutive weeks.The water intake was recorded at 1,4,and 8 weeks.HE staining was employed to observe the pathological changes of the submandibular gland tissue.ELISA was used to compare the serum levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).Western blot was used to detect the protein expression of PI3K-Akt pathway.Results Through network pharmacology screening,the top 7 core active components of Shengxian Buye Decoction for treating SS were quercetin,kaempferol,luteolin,β-sitosterol,stigmasterol,formononetin and wogonin,with 101 corresponding therapeutic targets.The top 5 targets were IL6,IL1B,TNF,AKT1,and MMP9.These key targets were mainly enriched in the PI3K-Akt,MAPK,and TNF signaling pathways.Animal experiment results showed that,compared with the model group,the water intake of mice in the Chinese materia medica group and Western medicine group significantly decreased at 4 and 8 weeks after treatment(P<0.05);focal lymphoid cell aggregation in the submandibular gland tissue of mice decreased;the serum contents of inflammatory factors IL-6 and TNF-α were significantly reduced(P<0.05);the expressions of p-PI3K,PI3K,p-Akt,and Akt proteins of the submandibular gland were up-regulated(P<0.05).Conclusion Shengxian Buye Decoction may exert anti-inflammatory and immune-regulating effects to treat SS by regulating signaling pathways such as PI3K-Akt,MAPK,and TNF.