升陷乌梅汤对激素干预哮喘大鼠TGF-β1/Smad信号通路及气道重塑的影响  

Effect of Shengxian Wumei decoction on TGF-β1/Smad signaling pathway and airway remodeling in asthma rat model with glucocorticoids intervention

作　　者：任培中 陈秋仪 王佳美 弓雪峰 崔红生 REN Peizhong;CHEN Qiuyi;WANG Jiamei;GONG Xuefeng;CUI Hongsheng(Department of Respiratory Medicine,Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学第三附属医院呼吸科,北京100029

出　　处：《上海中医药杂志》2020年第3期85-90,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81273689);北京市科委首都特色资助项目(Z161100000516055)。

摘　　要：目的观察升陷乌梅汤对激素干预哮喘大鼠TGF-β1/Smad信号通路和气道重塑的影响。方法将50只健康雄性SD大鼠随机分为正常组、哮喘组、激素组、布地奈德组、升陷乌梅汤组。除正常组外,其余各组采用卵蛋白致敏、雾化激发建立哮喘大鼠模型,并予各给药组大鼠腹腔注射糖皮质激素干预,在此基础上予升陷乌梅汤组大鼠灌胃、布地奈德组大鼠雾化吸入。观察各组大鼠肺功能及支气管病理改变,并采用Western blot及RT-qPCR法检测TGF-β1/Smad信号通路相关因子蛋白及mRNA表达的变化。结果①与正常组比较,哮喘组大鼠肺组织中胶原蛋白表达、WAi/Pbm、WAm/Pbm及WAe/Pbm升高(P<0.05),信号通路因子TGF-β1、Smad2、Smad3的蛋白和mRNA表达及p-Smad2、p-Smad3的蛋白表达均升高(P<0.05),而肺功能中FEV0.1、FEV0.1/FVC、FEF50%及FEF75%均降低(P<0.05),肺组织中Ai/Pbm以及通路因子Smad6、Smad7的蛋白和mRNA表达均降低(P<0.05)。②与哮喘组比较,各给药组均可减少肺组织中WAi/Pbm、WAm/Pbm和WAe/Pbm(P<0.05),降低TGF-β1、Smad2、Smad3的mRNA表达及TGF-β1、Smad2、p-Smad2、p-Smad3的蛋白表达(P<0.05),并升高FEV0.1、FEV0.1/FVC、FEF50%和FEF75%(P<0.05),增加Smad6、Smad7的mRNA表达(P<0.05);且升陷乌梅汤组较激素组可进一步减少WAi/Pbm、WAm/Pbm、WAe/Pbm,降低TGF-β1、Smad2、Smad3的蛋白和mRNA表达及p-Smad2、p-Smad3的蛋白表达(P<0.05),并升高FEV0.1、FEV0.1/FVC、FEF75%,增加Smad6的蛋白和mRNA表达以及Smad7的mRNA表达(P<0.05)。结论升陷乌梅汤可在激素干预基础上进一步阻止TGF-β1/Smad信号通路的异常激活,抑制气道重塑发展,延缓肺功能下降。Objective To observe the effect of Shengxian Wumei decoction(SXWMD)on airway remodeling and TGF-β1/Smad signaling pathway in asthmatic rat model treated with glucocorticoids.Methods Totally 50 SD male rats were randomly divided into normal group,asthma group,glucocorticoids intervened group,budesonide group and SXWMD group.The asthma model was established by sensitization and atomization stimulation with ovalbumin(OVA).Except rats in the normal group and asthma group,all of the others were intraperitoneally injected with glucocorticoids.Based on the glucocorticoids intervention,rats in the budesonide group were administered with budesonide by atomization,and rats in the SXWMD group were treated with intragastric administration of SXWMD.Lung function indexes and pathological changes of bronchus were measured.The expression levels of TGF-β1/Smad signaling pathway related indexes were detected by Western blot and RT-qPCR.Results①Compared with the normal group,the levels of collagen,WAi/Pbm,WAm/Pbm and WAe/Pbm,the protein and mRNA levels of TGF-β1,Smad2 and Smad3,and the protein levels of p-Smad2 and p-Smad3 were significantly increased(P<0.05),while the levels of FEV0.1,FEV0.1/FVC%,FEF50%and FEF75%,the Ai/Pbm,and the protein and mRNA levels of Smad6 and Smad7 were significantly decreased(P<0.05)in the asthma group.(2)Compared with the asthma group,the levels of WAi/Pbm,WAm/Pbm and WAe/Pbm,the mRNA levels of TGF-β1,Smad2,and Smad3,and the protein levels of TGF-β1,Smad2,p-Smad2 and p-Smad3 were significantly decreased(P<0.05),while the levels of FEV0.1,FEV0.1/FVC,FEF50%and FEF75%,and the mRNA levels of Smad6 and Smad7 were significantly increased(P<0.05)in all intervened groups.In addition,in the SXWMD group,the levels of WAi/Pbm,WAm/Pbm and WAe/Pbm,the protein and mRNA levels of TGF-β1,Smad2,and Smad3,and the protein levels of p-Smad2 and p-Smad3 were further decreased than those in the glucocorticoids intervened group(P<0.05),while the levels of FEV0.1,FEV0.1/FVC and FEF75%,the protein and mRNA levels of Sma

关 键 词：升陷乌梅汤 哮喘 TGF-Β1/SMAD信号通路 激素干预 气道重塑 大鼠 

分 类 号：R285.5[医药卫生—中药学]