哮喘大鼠TGF-β1/Smad3信号通路中黄芪与激素调控的对比研究  

Regulation of Glucocorticoids and Radix Astragali Comparison study of TGF-β1/Smad3 Signal Pathway on Airway Remodelling in Asthma Rats

作　　者：戴欢[1] 张维溪[1] 贺孝良[1] 赵瑞雪[1] 方丽[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内科,浙江温州325027

出　　处：《中华中医药学刊》2011年第12期2645-2648,I0020,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(30571981)

摘　　要：目的:观察黄芪、糖皮质激素对哮喘大鼠TGF-β1/Smad3信号通路及哮喘气道重塑的对比调控作用。方法SPF级雄性SD大鼠50只随机分为5组,分别为对照组(A组)、哮喘组(B组)、布地奈德组(C组)、地塞米松组(D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;免疫组化法检测肺组织TGF-β1、P-Smad3蛋白的表达;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。结果:干预组大鼠Wat、Wam较哮喘组显著性降低(均P<0.01),C组、D组Wat比较无显著性差异,但均低于黄芪组(均P<0.01);C组、D组Wam比较无显著性差异,D组Wam较F组有降低;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。干预组TGF-β1的蛋白表达均显著低于哮喘组(P<0.05或P<0.01);C组、D组、F组比较无显著性差异,P-Smad3蛋白表达:各干预组均显著低于哮喘组(均P<0.01),C组、F组之间无显著性差异,D组较F组降低(P<0.01);干预组血清、BALF中TGF-β1浓度与哮喘组比较有降低(均P<0.01),BALF中C组、D组、F组比较无显著性差异,血清中C组、D组无显著性差异,但均低于F组(P<0.05或P<0.01)。结论糖皮质激素、黄芪可通过调控TGF-β1/Smad3信号通路而拮抗气道重塑,但黄芪效果比糖皮质激素稍差。Objective ： The regulation of Glucocorticoids and Radix Astragali （RA） toTGF - β1/Smad3 signal pathway and asthma airway remodeling was observed. Methods ： In the experiment, 50 male Sprague - Dawlay （SD） rats, grade SPF were needed. 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 BUD（ group C） ,treaded group with DXM（ group D）, treated group with RA （group F）. Every group has ten rats. The total brochial wall thickness （Wat） and the airway smooth muscle thickness （Warn） 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 concentrations of TGF - β1 in serum and BALF were tested by sandwich ELISA. Results：Compared with group B,Wat and Warn of treated groups were significantly decreased（P 〈0.01 ） ,group C and D were lower than group F. The protein expression of TGF - β1 was obviously consistent with that of P - Smad3. Protein expressions of TGF - β1 and P - Smad3 in treated groups were significantly elevated compared with group B, group C and D were significantly lower than group F （P 〈 0. 01 ）. The concentrations of TGF- β1 in serum and BALF： treated groups were significantly decreased than group B, in BALF, group Cnad group D were the same with group F, but in serum, group C and group D were lower than group F. Conclusions ： BUD, DXM and Ra- dix Astragali （RA） markedly reduce the airway inflammation,inhibit and improve the airway remodeling, which is possibly partly through regulating TGF - β1/Smad3 pathway, but Glucocorticoids were better effective than RA.

关 键 词：哮喘 气道重塑 转化生长因子-Β1 SMAD3 糖皮质激素 黄芪 

分 类 号：R256.12[医药卫生—中医内科学]