黄芪在哮喘大鼠气道重塑模型中对TGF-β1/Smad3信号通路的调控

Effect of TGF-β1/Smad3 Signal Pathway on Airway Remodelling in Asthma Rats with the Regulation of Radix Astragali

目的:研究转换生长因子β1(TGF-β1)/Smad3信号通路在哮喘气道重塑中的作用,探讨黄芪对TGF-β1/Smad3信号通路及哮喘气道重塑的调控作用。方法:SPF级雄性SD大鼠30只随机分为3组,分别为对照组(A组)、哮喘组(B组)、黄芪组(F组),每组10只。用卵白蛋白(OVA)致敏与激发建立大鼠哮喘模型。应用图像分析技术测定肺内支气管壁厚度(Wat)及平滑肌厚度(Wam)等重塑指标;免疫组化法及RT-PCR法检测肺组织TGF-β1、P-Smad3蛋白及mRNA的表达。结果:哮喘组大鼠Wat、Wam较对照组显著增加(均P<0.01),黄芪组与哮喘组比较有显著降低(均P<0.01),但仍高于对照组(P<0.01);免疫组化染色阳性结果呈棕黄色,TGF-β1蛋白表达于胞浆,P-Smad3蛋白表达于胞浆和胞核,主要表达于支气管上皮细胞、平滑肌细胞、成纤维细胞及散在的炎性细胞。哮喘组TGF-β1和P-Smad3的蛋白表达均显著高于对照组(均P<0.01);黄芪组TGF-β1、P-Smad3的蛋白表达均显著低于哮喘组(均P<0.01),但仍高于对照组(均P<0.01)。肺组织中TGF-β1 mRNA及Smad3 mRNA表达:哮喘组TGF-β1和P-Smad3的蛋白表达均显著高于对照组(均P<0.01);黄芪组TGF-β1、P-Smad3的蛋白表达均显著低于哮喘组(均P<0.01),但仍高于对照组(均P<0.01)。结论:TGF-β1/Smad3信号通路参与了哮喘气道重塑过程,黄芪可通过调控TGF-β1/Smad3信号通路而拮抗气道重塑。

Objective： To study the role of TGF-β1/ Smad3 signal pathway in airway remodeling of asthma rats and to observe the regulation of Radix Astragali（RA） toTGF-β1/ Smad3 signal pathway and asthma airway remodeling.Methods：In the experiment,30 male Sprague-Dawlay（SD） rats,grade SPF.Asthmatic airway remodelling model rats were sensitized with ovalbumin and AL（OH）3,and repeatedly exposed to aerosolized ovalbumin.According to the repeated time course of challenge,rats were randomly divided into the control group（group A）,asthma group（group B） and treated group with RA（group F）.Every group has ten rats.The total brochial wall thickness（Wat） and the airway smooth muscle thickness（Wam） were measured by image analysis system.The protein expressions of TGF-β1 and P-Smad3 in the lung tissues were detected by immunohistochemistry technique.The mRNA expressions of TGF-β1 and Smad3 in the lung tissues were detected by RT-PCR.Results： Compared with group A,Wat and Wam of group B significantly increased（P0.01）;compared with group B,group F were significantly decreased（P0.01）;The protein expression of TGF-β1 was obviously consistent with that of P-Smad3.Protein expressions of TGF-β1 and P-Smad3 in groups B were significantly elevated compared with those of group A,Group F were significantly lower than those of group B（P0.01）,but were significantly increased compared with group A（P0.01）.Expression of TGF-β1 mRNA was obviously consistent with that of Smad3 mRNA.Expression of TGF-β1 mRNA and Smad3 mRNA in groups B were significantly elevated compared with those of group A（P0.01）.Group F were significantly lower than those of group B（P0.01）,but were significantly increased compared with group A（P0.01）.Conclusion：1.The expressions of TGF-β1 and Smad3 in rats of asthma airway remodeling are increased,which implicate that TGF-β1/ Smad3 signal transduction pathway plays an important role in the airway remodeling of asthma;2.Radix Astragali（RA） markedly reduces the airway inflammation,inhibits and improves the airway remodeling are possibly partly through regulating TGF-β1/ Smad3 pathway.