蒲公英甾醇通过调节Wnt/β-catenin信号通路抑制转化生长因子β_(1)对肺纤维化的改善作用  

Taraxasterol modulates the Wnt/β-catenin signaling pathway to inhibit the improvement of pulmonary fibrosis induced by transforming growth factorβ_(1)

作　　者：邱慧萍[1] 樊丹丹 张莉 QIU Huiping;FAN Dandan;ZHANG Li(Department of Oncology,Jiangxi Chest Hospital,Jiangxi Province,Nanchang 330000,China)

机构地区：[1]江西省胸科医院肿瘤科,江西南昌330000

出　　处：《中国当代医药》2024年第35期16-22,共7页China Modern Medicine

基　　金：江西省中医药管理局科技计划项目(2023B1299)。

摘　　要：目的探究肺纤维化的发病机制,并验证蒲公英甾醇(TAR)抗肺纤维化作用的有效性,特别是通过调节Wnt/β-连环蛋白信号通路(Wnt/β-catenin)和转化生长因子β_(1)(TGF-β_(1))诱导的肺泡上皮细胞表型转化(EMT)过程。方法取40只小鼠分为四组,每组各10只。A组不进行任何处理;B组腹腔注射博来霉素构建肺纤维化模型;C组肺纤维化模型使用XAV-939干预;D组肺纤维化模型使用TAR干预。同时使用Wnt3a信号蛋白处理肺成纤维细胞和肺泡上皮细胞以构建细胞模型。随后利用不同浓度的TAR进行干预,采用HE染色、Masson三色染色、Western blot、实时荧光定量PCR和酶联免疫吸附试验(ELISA)等方法,分析各组小鼠及细胞模型中相关指标的表达变化。结果B组的α1(Ⅰ)型前胶原、α-平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶组织抑制因子1(TIMP-1)、基质金属蛋白酶2(MMP-2)、Smad家族成员3(Smad3)、细胞周期蛋白D1(cyclinD1)、β-连环蛋白的表达水平均高于A组,差异有统计学意义(P<0.05)。B组的Smad家族成员7(Smad7)的表达水平低于A组,差异有统计学意义(P<0.05)。B组的TGF-β_(1)、结缔组织生长因子(CTGF)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)表达水平均高于A组,差异有统计学意义(P<0.05)。D组的上述指标均低于B组,差异有统计学意义(P<0.05)。结论TAR能有效抑制小鼠肺纤维化模型中的纤维化标志物和炎症因子的表达,其作用可能通过调节Wnt/β-catenin信号通路和抑制TGF-β_(1)诱导的EMT过程实现。Objective To elucidate the pathogenesis of pulmonary fibrosis and evaluate the efficacy of taraxasterol(TAR)in attenuating pulmonary fibrosis,particularly by modulating the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition(EMT)process induced by transforming growth factorβ_(1)(TGF-β_(1)).Methods A total of 40 mice were divided into four groups,with 10 mice in each group.Group A received no treatment.Group B was administered bleomycin via intraperitoneal injection to establish a pulmonary fibrosis model.The pulmonary fibrosis model in Group C was intervened with XAV-939.The pulmonary fibrosis model in Group D was intervened with TAR.Concurrently,pulmonary fibroblasts and alveolar epithelial cells were treated with Wnt3a signaling protein to construct a cellular model.Then,different concentrations of TAR were used for intervention.The expression changes of relevant indicators in the various groups of mice and cell models were analyzed using methods including HE staining,Masson's trichrome staining,Western blot,real-time quantitative PCR,and enzyme-linked immunosorbent assay(ELISA).Results the expression levels of procollagenα1(Ⅰ),alpha-smooth muscle actin(α-SMA),tissue inhibitor of metalloproteinase-1(TIMP-1),matrix metalloproteinase-2(MMP-2),Smad family member 3(Smad3),cyclin D1(cyclinD1),andβ-catenin in Group B were higher than those in Group A,with statistically significant differences(P<0.05).The expression level of Smad family member 7(Smad7)in Group B was lower than that in Group A,with statistically significant difference(P<0.05).The expression levels of TGF-β_(1),connective tissue growth factor(CTGF),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)in Group B were higher than those in Group A,with statistically significant differences(P<0.05).The above indexes in Group D were lower than those in Group B,with statistically significant differences(P<0.05).Conclusion TAR effectively inhibits the expression of fibrosis markers and inflammatory factors in a mouse model

关 键 词：肺纤维化 蒲公英甾醇 Wnt/β-连环蛋白信号通路 转化生长因子β_(1) 小鼠 

分 类 号：R563[医药卫生—呼吸系统] R966[医药卫生—内科学]