复明汤调控TGF-β1/Smad3通路抑制肺成纤维细胞活化及肺上皮损伤减轻博来霉素诱导的肺纤维化  

Fuming decoction inhibits the activation of lung fibroblast and lung epithelial injury to alleviate bleomycin-induced pulmonary fibrosis through regulating TGF-β1/Smad3 pathway

作　　者：余洪刚 付大海 杨利生 宋超 唐俊峰[2] 秦晓娟[3] YU Honggang;FU Dahai;YANG Lisheng;SONG Chao;TANG Junfeng;QIN Xiaojuan(Department of Pulmonary Diseases,Xi’an Hospital of Traditional Chinese Medicine,Xi’an 710012,China;Department of Traditional Chinese Medicine Pharmacology,Shaanxi University of Chinese Medicine,Xianyang 712000,China;Department of Respiratory Medicine,Hanzhong People’s Hospital,Hanzhong 723000,China)

机构地区：[1]西安市中医医院肺病科,西安710012 [2]陕西中医药大学中药药理学研究室,咸阳712000 [3]汉中市人民医院呼吸内科,汉中723000

出　　处：《天津中医药》2020年第12期1412-1419,共8页Tianjin Journal of Traditional Chinese Medicine

基　　金：西安市科技计划项目(201805103YX11SF37)。

摘　　要：[目的]探讨复明汤用于肺纤维化治疗的具体作用机制,为其临床应用奠定理论基础。[方法]通过荧光素酶报告基因检测复明汤对转达化生长因子β1(TGF-β1)信号通路的影响,采用蛋白印记法(Western blot)检测其对TGF-β1诱导的Smad2/3依赖途径和肺Smad信号传导的影响;实时荧光定量聚合酶链反应(qRT-PCR)及Western blot法检测复明汤对细胞外基质(ECM)相关mRNA和蛋白水平及上皮损伤相关mRNA和蛋白的影响,最终构建小鼠肺纤维化模型,明确复明汤对小鼠肺纤维化的治疗效果。[结果]复明汤可拮抗TGF-β1/Smad3信号传导,其不仅可抑制TGF-β1诱导的肺泡上皮细胞损伤,而且可降低TGF-β1诱导的成纤维细胞分化、细胞外基质生成和成纤维细胞迁移。体内实验表明复明汤可抑制博来霉素诱导的肺损伤,甚至减弱小鼠中已成形的肺纤维化。[结论]复明汤可通过介导TGF-β1/Smad3通路减轻博来霉素诱导的小鼠肺纤维化,为复明汤治疗肺纤维化的临床应用奠定理论基础。[Objective]To explore the mechanism of Fuming decoction in the treatment of pulmonary fibrosis,and to lay a theoretical foundation for its clinical application.[Methods]The effect of Fuming decoction on TGF-β1 signaling pathway was detected by luciferase reporter gene,and its effect on TGF-β1-induced Smad2/3-dependent pathway and non-Smad signaling was detected,qRT-PCR and western blot methods were used to detect the effect of fuming decoction on the levels of ECM-related mRNA and protein and epithelial damage-related mRNA and protein.Finally,mouse lung fibrosis model was established to clarify the therapeutic effect of fuming decoction on pulmonary fibrosis.[Results]Fuming decoction can antagonize TGF-β1/Smad3 signaling,which can not only inhibit TGF-β1-induced alveolar epithelial cell damage,but also reduce TGF-β1-induced fibroblast differentiation,extracellular matrix formation and fibroblast migration.In vivo experiments showed that Fuming decoction could inhibit bleomycin-induced lung injury and even attenuate formed pulmonary fibrosis in mice.[Conclusion]Fuming decoction can alleviate bleomycin-induced pulmonary fibrosis in mice by mediating the TGF-β1/Smad3 pathway,which lays a theoretical foundation for the clinical application of fuming decoction in the treatment of pulmonary fibrosis.

关 键 词：复明汤 转化生长因子-β1 SMAD3 肺纤维化 

分 类 号：R563.9[医药卫生—呼吸系统]