糖皮质激素调控哮喘大鼠气道重塑中TGF-β_1/Smad信号通路的研究  

Effects of glucocorticoids on TGF-β_1/Smad signal pathway in airway remodeling of asthma rats

作　　者：张维溪[1] 戴欢[1] 贺孝良[1] 方丽[1] 赵瑞雪[1] 李昌崇[1] 

机构地区：[1]温州医学院附属育英儿童医院呼吸科,浙江温州325027

出　　处：《中国药理学通报》2009年第9期1142-1146,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30571981);温州市科技计划资助项目(NoY20041046)

摘　　要：目的观察糖皮质激素对哮喘大鼠气道重塑中转换生长因子β1(TGF-β1)/Smad信号通路的作用。方法以卵清白蛋白(OVA)致敏与激发建立哮喘大鼠气道重塑模型。SPF级♂SD大鼠40只分为对照组(A组)、哮喘组(B组)、布地奈德组(C组)和地塞米松干预组(D组),每组10只。应用酶联免疫吸附试验(ELISA)法测定血清和支气管肺泡灌洗液(BALF)中TGF-β1的浓度,免疫组化法检测肺组织TGF-β1、P-Smad2、P-Smad3、Smad6和Smad7蛋白的表达。结果与A组比较,B组支气管壁厚度(Wat)、平滑肌厚度(Wam)、血清、BAFL中TGF-β1的浓度、P-Smad2和P-Smad3的蛋白表达均增高,Smad6、Smad7的蛋白表达低于A组,经布地奈德组和地塞米松干预后,Wat、Wam、血清、BAFL中TGF-β1的浓度、TGF-β1、P-Smad2和P-Smad3的蛋白表达均下降,Smad6、Smad7的蛋白表达增强。C组和D组Wat、Wam、血清、BAFL中TGF-β1的浓度、TGF-β1P-Smad2、P-Smad3、Smad6和Smad7的蛋白表达比较无明显差异。免疫组化显示TGF-β1和Smad6蛋白表达于胞质,Smad7、P-Smad3和P-Smad2蛋白表达于胞质和胞核,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。大鼠肺组织中Smad6蛋白和Smad7蛋白表达呈正相关,P-Smad2蛋白和P-Smad3蛋白表达呈正相关。结论糖皮质激素可通过调控TGF-β1/Smad信号通路而拮抗哮喘气道重塑。Aim To observe the effects of glucocorti-coids（ GCs ） on TGF-β1Smad signal pathway in airway remodeling of asthma rats. Methods Asthmatic airway remodeling model rats were sensitized with ovalbumin and AL （OH）3, and repeatedly exposed to aerosolized ovalbumin. 40 male Sprague-Dawlay （ SD ） rats, grade SPF, were randomly divided into control group （ group A ）, asthma group （ group B ）, treated group with Budesonide （group C ） and treated group with dexamethasone （group D）. The concentrations of TGF-β1 in serum and BALF were tested by sandwich ELISA. The protein expressions of TGF-β1, P-Smad 2, P-Smad 3, Smad 6 and Smad 7 in the lung tissues were detected by immunohistochemistry technique. Results Compared with group A, the results of Wat and Warn, the concentrations of TGF-β1 in serum and BALF were higher, the protein expressions of TGF-β1, P- Smad ：2 and P-Smad 3 were also rised in group B. The protein expressions of Smad 6 and Smad 7 of group B were lower than those in group A. The results of Wat and Wam, the concentrations of TGF-β1 in serum and BALF were decreased in group C and group D. The protein expressions of TGF-β1 ,P-Smad 2 and P-Smad 3 were also decreased in group C and group D. The protein expressions of Smad 6 and Smad 7 of group C and group D were higher than those in group B. There were no significant difference with the results of Wat and Warn, the concentrations of TGF-β1 in serum and BALF, the protein expressions of TGF-β1, P-Smad 2, P- Smad 3, Smad 6 and Smad 7 between group C and group D. The protein of TGF-β1 and Smad 6 were expressed in cytoplasm, Smad 7, P-Smad 3 and P-Smad2 were expressed in cytoplasm and nuclear. They were mainly expressed in bronchial epithelial cells, smooth muscle cells, fibroblast cells and interspersed inflammatory cells. There was a correlation between the protein expressions of P-Smad 2 those of P-Smad 3 in lung tissues. There was correlation between the protein expressions of Smad 6 and those of Smad 7 in lung tissues. Conc

关 键 词：糖皮质激素 哮喘 气道重塑 信号转导 转化生长因子-β1 SMAD 大鼠 

分 类 号：R-332[医药卫生] R322.33