人参皂苷Rb1通过调控Wnt3/β-catenin通路对结缔组织并发间质性肺炎大鼠肺纤维化的影响  

The effect of ginsenoside Rb1 on pulmonary fibrosis in rats with interstitial pneumonia by regulating the Wnt3/β-catenin pathway

作　　者：桑娟 刘凡 SANG Juan;LIU Fan(Wuhan Hospital of China University of Geosciences,Wuhan 430074,Hubei,China)

机构地区：[1]中国地质大学(武汉)医院,湖北武汉430074

出　　处：《贵州医科大学学报》2025年第1期48-56,共9页Journal of Guizhou Medical University

基　　金：湖北省中医药管理局中医药科研项目(ZY2023F053)。

摘　　要：目的探究人参皂苷Rb1通过调控Wnt3/β-catenin通路对改善结缔组织并发间质性肺炎大鼠肺纤维化的作用机制。方法85只大鼠随机分为假手术组、模型组、人参皂苷Rb1组、Wnt3/β-catenin激活剂(HLY78)组及人参皂苷Rb1+HLY78组,每组17只;除假手术组外的4组大鼠均采用博来霉素法诱导建立大鼠间质性肺炎模型,各组随机选择2只大鼠评价造模是否成功,采用BUXCO动物肺功能分析系统和ELISA法检测大鼠肺功能、血清炎症因子及纤维化因子水平;HE及Masson染色观察肺病理损伤形态;免疫荧光共定位法测β-catenin与肺成纤维细胞(标记抗体-FSP-1)及肺间充质干细胞(标记抗体-Nanog)共表达变化;Western blot法测Wnt3/β-catenint通路及下游纤维化相关蛋白表达。结果与假手术组相比,模型组大鼠呼吸困难、死亡、肺功能受损、纤维化加重等症状严重,β-catenin^(+)FSP-1^(+)及β-catenin^(+)Nanog^(+)表达升高,Wnt3/β-catenin通路活性升高(P<0.05);人参皂苷Rb1可缓解大鼠上述症状,并抑制Wnt3/β-catenin活性、降低β-catenin^(+)FSP-1^(+)及β-catenin^(+)Nanog^(+)表达(P<0.05);Wnt3/β-catenin激活剂-HLY78可减弱人参皂苷Rb1的上述作用(P<0.05)。结论人参皂苷Rb1可能通过抑制Wnt3/β-catenin通路在肺成纤维细胞及间充质干细胞中表达,阻断肌成纤维细胞转化,而延缓大鼠肺纤维化进程。Objective To explore the mechanism of ginsenoside Rb1 and its effect on pulmonary fibrosis of connective tissues in rats with interstitial pneumonia by regulating the Wnt3/β-catenin pathway.Methods Eighty-five rats were randomly divided into the sham operation group,the model group,the ginsenoside Rb1 group,Wnt3/β-catenin activator(HLY78)group,and the ginsenoside Rb1+HLY78 groups,with 17 cases in each group.Interstitial pneumonia models were established by bleomycin therapy in all the 4 groups except the sham operation group,and 2 rats were randomly selected from each group to show if the modeling was successful.The lung function,serum inflammatory factor and fibrosis factor level were measured by BUXCO animal lung function analysis system and ELISA;HE and Masson staining to observe lung pathological damage;immunofluorescence co-localization method to detectβ-catenin and lung fibroblasts(labeled antibody-FSP-1)and lung Co-expression changes in mesenchymal stem cells(labeled antibody-Nanog).Western blot was used to detect the expression of Wnt3/β-catenint pathway and downstream fibrosis-related proteins.Results Compared with the sham operation group,the model group had severe symptoms including dyspnea,death,impaired lung function,and aggravated fibrosis.The expression ofβ-catenin~+FSP-1~+andβ-catenin~+Nanog~+increased,and Wnt3/β-catenin pathway activity also increased(P<0.05).Ginsenoside Rb1 could alleviate the above-mentioned symptoms,inhibit the activity of Wnt3/β-catenin,and reduce the expression ofβ-catenin~+FSP-1~+andβ-catenin~+Nanog~+(P<0.05).Wnt3/β-catenin activator-HLY78 could attenuate the above-mentioned effects of ginsenoside Rb1(P<0.05).Conclusion Ginsenoside Rb1 may inhibit the expression of Wnt3/β-catenin pathway in lung fibroblasts and mesenchymal stem cells,block myofibroblast transformation,and delay the process of pulmonary fibrosis in rats with connective tissue disease complicated by interstitial pneumonia.

关 键 词：人参皂苷RB1 结缔组织并发间质性肺炎 基质细胞衍生因子-1 趋化因子受体-4 肺纤维化 

分 类 号：R563[医药卫生—呼吸系统] R285.5[医药卫生—内科学]