卡介苗对支气管哮喘大鼠气道重塑的作用及机制  

Therapeutic effects of Bacille Calmette-Guerin vaccine on asthma airway remodeling in rats and its mechanism

作　　者：加慧 薄建萍[1] 刘晨涛[1] 常琴[1] 董艳婷[1] 田新瑞[1] 

机构地区：[1]山西医科大学第二医院呼吸内科,太原030001

出　　处：《中华医学杂志》2014年第8期617-621,共5页National Medical Journal of China

基　　金：山西省自然科学基金（2013011055-1）

摘　　要：目的 探讨卡介苗对支气管哮喘（简称哮喘）大鼠气道重塑的作用及机制.方法Wistar雄性大鼠40只按随机数字表法分为对照组、哮喘组、卡介苗组、地塞米松组、卡介苗＋地塞米松组各8只.以卵白蛋白建立哮喘气道重塑模型,激发前30 min卡介苗组给予皮下注射卡介苗 0.025 mg,地塞米松组腹腔注射地塞米松0.5 mg/kg,卡介苗＋地塞米松组腹腔注射地塞米松0.25 mg/kg,皮下注射卡介苗 0.025 mg,对照组以生理盐水代替卵白蛋白腹腔注射及雾化吸入.计算机图像分析气道重塑程度,并检测支气管肺泡灌洗液（BALF）及血清中转化生长因子β1（TGF-β1）含量及肺组织中E钙黏蛋白、α平滑肌肌动蛋白（α-SMA）、纤维连接蛋白的表达,并进行统计学对比分析.结果 哮喘组大鼠气道壁、平滑肌厚度[（95.01±0.48）、（43.86±0.51）μm]显著厚于对照组[（25.96±0.42）、（15.14±0.18）μm],BALF、血清TGF-β1含量[（10.05±0.26）、（75.67±1.17）μg/L]显著高于对照组[（1.53±0.18）、（22.24±0.35）μg/L],E钙黏蛋白表达（0.26±0.03）显著低于对照组（0.45±0.04）,α-SMA、纤维连接蛋白表达（0.54±0.06、0.56±0.06）显著高于对照组（0.32±0.04、0.35±0.06）（均P〈0.01）.卡介苗组、地塞米松组、卡介苗＋地塞米松组治疗后气道壁和平滑肌厚度分别为（58.46±2.43）、（49.51±1.44）、（49.63±1.42）μm和（25.84±0.54）、（25.44±0.40）、（25.62±1.17）μm,BALF和血清 TGF-β1含量分别为（3.42±0.18）、（3.27±0.34）、（3.39±0.26）μg/L和（37.61±0.22）、（35.65±0.49）、（36.22±0.71）μg/L,均显著低于哮喘组（均P＜0.01）;E钙黏蛋白表达（0.29±0.04、0.32±0.04、0.31±0.03）显著高于哮喘组,α-SMA和纤维连接蛋白表达（0.40±0.06、0.35±0.06、0.40±0.05和0.47±0.03、0.43±0.06、0.47±0.04）均显著低于哮喘组（均P〈0.01）.Western印迹结果与上相似.结论 卡介苗通过�Objective To explore the therapeutic effects and mechanism of Bacillus Calmette- Guerin （BCG） vaccine on airway remodeling in rats. Methods Forty male Wistar rats were randomly divided into 5 groups of control, asthma, BCG vaccine, dexamethasone and BCG vaccine plus dexamethasone （ n = 8 each ）. The animals were then sensitized and challenged by ovalbumin to establish the asthmatic model. A subcutaneous injection of BCG vaccine 0. 025 mg was administered for the BCG vaccine group and an intraperitoneal injection of dexamethasone 0. 5 mg/kg for the dexamethasone group. In BCG vaccine plus dexamethasone group, the rats received a subcutaneous injection of BCG vaccine （ 0. 025 mg） plus an intraperitoneal injection of dexamethasone （0. 25 mg/kg）. All treatments were offered at half an hour pre- atomization. The control rats received an aerosol inhalation of normal saline instead of ovalbum. The parameters of airway morphological changes and the degree of airway remodeling were analyzed with computer graphics. The levels of transforming growth factor beta 1 （TGF-1） in bronchoalveolar lavage fluid （BALF） and the expressions of E-cadherin,a-smooth muscle actin （s-SMA） and fibronectin in lung tissue and sera were detected. Results In asthmatic rats, the thickness of airway wall and smooth muscle were more significant than those of the control group （ （ 95.01 ± 0. 48 ）, （ 43.86 ± 0. 51 ） vs （ 25.96 ± 0. 42 ）, （15.14±0. 18） μm）. Compared with the control group, the levels of TGF-β1 in BALF and sera were significantly higher （ （ 10.05 ±0. 26）, （ 75.67 ± 1.17 ） vs （ 1.53 ± 0. 18 ）, （ 22. 24 ±0. 35 ） μg/L）, the expression of E-cadherin significantly decreased （ 0. 26 ±0.03 vs 0. 45 ±0.04 ）, while a-SMA and fibronectin significantly increased （ 0. 54 ± 0.06,0. 56 ±0. 06 vs 0. 32 ±0. 04,0. 35 ± 0. 06 ） （ all P 〈 0. 01 ）; Notably, compared with the asthmatic group, the thickness of airway wall and smooth muscle （（58.46± 22.43�

关 键 词：哮喘 卡介苗 气道重塑 转化生长因子Β1 大鼠 

分 类 号：R562.25[医药卫生—呼吸系统]