宣肺开闭汤通过抑制TGF-β1/Smad3通路减缓小鼠肺纤维化进展  

Xuanfei Kaibi Decoction Slows Down the Progression of Pulmonary Fibrosis in Mice by Inhibiting the TGF-β1/Smad3Pathway

作　　者：孔维祎 郝欧美[2] 盛秋菊 KONG Wei-Yi;HAO Ou-Mei;SHENG Qiu-Ju(Liaoning University of Traditional Chinese Medicine,Shenyang 110032 Liaoning,China;The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032 Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110032 [2]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《广州中医药大学学报》2023年第12期3130-3138,共9页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：辽宁省自然科学基金资助项目(编号:2019-ZD-0788)。

摘　　要：【目的】探讨宣肺开闭汤对肺纤维化小鼠的治疗作用及机制。【方法】将60只小鼠随机分为空白组,模型组,宣肺开闭汤低、中、高剂量组及宣肺开闭汤高剂量+转化生长因子β1(TGF-β1)/Smads通路激活剂(SRI-011381)组,每组10只。除空白组,其余各组小鼠采用博来霉素诱导构建肺纤维化模型。干预结束后,采用苏木素-伊红(HE)染色法观察肺组织病理学变化并进行炎症评分,马松(Masson)染色法观察肺组织纤维化改变并进行纤维化评分,免疫组织化学染色法观察肺组织中α-平滑肌肌动蛋白(α-SMA)表达,酶联免疫吸附分析(ELISA)检测肺组织中Hyp含量,蛋白印迹法(Western Blot)检测肺组织中TGF-β1、Smad3的蛋白表达,实时聚合酶链反应(RT-PCR)法检测肺组织中TGF-β1、Smad3的mRNA表达。【结果】与空白组比较,模型组小鼠肺泡腔炎症评分、肺纤维化评分、肺组织中α-SMA阳性表达水平、Hyp含量及TGF-β1、Smad3的蛋白和mRNA表达水平均显著升高(P<0.05);宣肺开闭汤低、中、高剂量组小鼠肺泡腔炎症评分、肺纤维化评分、肺组织中α-SMA阳性表达水平、Hyp含量及TGF-β1、Smad3的蛋白和mRNA表达水平均低于模型组,且呈剂量依赖性(P<0.05);与宣肺开闭汤高剂量组比较,宣肺开闭汤高剂量+SRI-011381组小鼠肺泡腔炎症评分、肺纤维化评分、肺组织中α-SMA阳性表达水平、Hyp含量及TGF-β1、Smad3的蛋白和mRNA表达水平均显著升高(P<0.05)。【结论】宣肺开闭汤可减轻博来霉素诱导的小鼠肺纤维化,其作用机制与抑制TGF-β1/Smad3信号通路有关。Objective To investigate the therapeutic effect and mechanism of Xuanfei Kaibi Decoction on mice with pulmonary fibrosis.Methods Sixty mice were randomly divided into blank group,model group,Xuanfei Kaibi Decoction low-,medium-and high-dose groups and Xuanfei Kaibi Decoction high-dose+transforming growth factorβ1(TGF-β1)/Smads pathway activator(SRI-011381)group,10 mice in each group.Except for the blank group,the remaining groups of mice were induced with bleomycin to construct the lung fibrosis model.At the end of the intervention,hematoxylin-eosin(HE)staining was used to observe pathological changes in lung tissue and score inflammation,Masson staining was used to observe fibrotic changes in lung tissue and score fibrosis,immunohistochemical staining was used to observe the expression ofα-smooth muscle actin(α-SMA)in lung tissue,enzyme-linked immunosorbent assay(ELISA)was used to detect the Hyp content in lung tissue,protein expressions of TGF-β1 and Smad3 in lung tissue by Western Blot,and mRNA expressions of TGF-β1 and Smad3 in lung tissue by real-time polymerase chain reaction(RT-PCR).Results Compared with the blank group,the alveolar inflammation score,lung fibrosis score,α-SMA positive expression level,Hyp content,and protein and mRNA expression levels of TGF-β1 and Smad3 were significantly increased in the model group(P<0.05);the alveolar inflammation score,lung fibrosis score,α-SMA positive expression level,Hyp content,and protein and mRNA expression levels of TCF-β1 and Smad3 in the Xuanfei Kaibi Decoction low-,medium-,and high-dose groups were lower than those of the model group,in a dose-dependent manner(P<0.05).Compared with the high dose group of Xuanfei Kaibi Decoction,the alveolar lumen inflammation score,lung fibrosis score,α-SMA positive expression level,Hyp content,and protein and mRNA expression levels of TGF-β1 and Smad3 in the high-dose of Xuanfei Kaibi Decoction+SRI-011381 group of mice were all significantly improved(P<0.05).Conclusion Xuanfei Kaibi Decoction can reduce bleomyc

关 键 词：宣肺开闭汤 肺纤维化 TGF-β1/Smad3信号通路 博来霉素 小鼠 

分 类 号：R285.5[医药卫生—中药学]