中药药理与临床2025，Vol.41Issue(9)：52-58,7.
归芪补肺汤联合来氟米特通过WNT/β-catenin信号通路对类风湿关节炎并间质性肺疾病上皮-间质转化的影响
Effect of Guiqi Bufei(归芪补肺)Decoction Combined with Leflunomide on Epithelial-Mesenchymal Transition(EMT)via Regulating Wnt/β-catenin Signaling Pathway in RA-ILD
摘要
Abstract
Objective:To investigate the effect of Guiqi Bufei(归芪补肺)Decoction on epithelial-mesenchymal transition(EMT)via regulating Wnt/β-catenin signaling pathway in rheumatoid arthritis-associated interstitial lung disease(RA-ILD).Methods:Sixty SD rats were random-ly divided into a normal control group(10 rats)and a modeling group(50 rats).RA-ILD model was established in the modeling group by collagen-induced arthritis(CIA)combined with bleomycin(BLM).After modeling,rats were randomly divided into model control group,1.78 g/kg methylprednisolone group,Guiqi Bufei Decoction groups of 4.29,8.57,and 17.14 g/kg,with 10 rats in each group.Except for the model control group,all treatment groups were administrated with 0.9 mg/kg Leflunomide.HE and Masson staining were performed to observe the pathological changes of lung tissue and evaluate the degree of alveolar inflammation and pulmonary fibrosis in each group.The serum con-tents of rheumatoid factor(RF),tumor necrosis factor α(TNF-α),anti-cyclic citrullinated peptide antibody(ANTI-CCP-AB),C-reactive protein(CRP),Transforming growth factor β1(TGF-β1),and matrix metalloproteinase 7(MMP7)were detected by ELISA.Immunohisto-chemistry and Western-blot were applied to detect the protein expressions of wingless type MMTV integration site family,member 5A(WNT5A),B-CATENIN,glycogen synthase kinase-3β(GSK3B),Phospho-GSK-3beta(SER9),MMP7,E-cadherin(CDH1),and actin al-pha 2(ACTA2)in lung tissue.RT-PCR was applied to detect the expression of Wnt5a,β-catenin,Gsk3β,Mmp7,Cdh1,and Actα2 genes in lung tissue.Results:Compared with those in the normal control group,the degree of alveolar inflammation and pulmonary fibrosis,the serum contents of RF,TNF-α,ANTI-CCP-AB,CRP,TGF-β1,and MMP7 were increased in the model control group,and the protein expressions of WNT5A,B-CATENIN,GSK3B,SER9,MMP7,CDH1,and ACTA2 in lung tissue were up-regulated,while the gene expressions of Wnt5a,β-catenin,Gsk3β,Mmp7,Cdh1,and Actα2 were also up-regulated(P<0.05).Compared with those in the model control group,the degree of alveolar inflammation and pulmonary fibrosis were decreased in the Guiqi Bufei Decoction groups of 8.57 and 17.14 g/kg,and the serum con-tents of RF,TNF-α,ANTI-CCP-AB,CRP,TGF-β1,and MMP7 were decreased.The protein expressions of WNT5A,B-CATENIN,GSK3B,SER9,MMP7,CDH1,and ACTA2 were down-regulated,and the gene expressions of Wnt5a,β-catenin,Gsk3β,Mmp7,Cdh1,and Actα2 were down-regulated(P<0.05).Conclusion:Guiqi Bufei Decoction can delay the development of pulmonary fibrosis by inhibiting the activation of the Wnt/β-catenin signaling pathway and regulating EMT.关键词
归芪补肺汤/类风湿关节炎并间质性肺疾病/类风湿关节炎/间质性肺疾病/无翅型MMTV整合位点家族成员5A/β-连环蛋白信号通路/上皮-间质转化Key words
Rheumatoid arthritis-associated interstitial lung disease/Rheumatoid arthritis/Interstitial lung disease/Guiqi Bufei(归芪补肺)Decoction/Wnt/β-catenin signaling pathway/Epithelial-mesenchymal transition引用本文复制引用
欧慧萍,林辉,袁多,莫玲岚,曾白玉,黄杏,范伏元..归芪补肺汤联合来氟米特通过WNT/β-catenin信号通路对类风湿关节炎并间质性肺疾病上皮-间质转化的影响[J].中药药理与临床,2025,41(9):52-58,7.基金项目
湖南省自然科学基金项目(编号:2023JJ60243) （编号:2023JJ60243）
湖南省中医药科研计划重点项目(编号:2021038) （编号:2021038）
湖南省教育厅科学研究项目(编号:19C1446) （编号:19C1446）
湖南中医药高等专科学校校级科研项目(编号:XY2022.006). （编号:XY2022.006）
