布地奈德早期干预对哮喘小鼠呼吸道炎症和白细胞介素-6/信号转导与转录激活因子3信号通路的影响  

Effects of Inhaled Budesonide in Early Phase on Airway Inflammation and Interleukin-6/Signal Transducers and Activators of Transcription 3 Signaling Pathway in Asthmatic Mouse

作　　者：刘艳明[1] 农光民[1] 李树全[2] 

机构地区：[1]广西医科大学第一附属医院儿科,南宁530021 [2]广西医科大学医学实验中心,南宁530021

出　　处：《实用儿科临床杂志》2010年第16期1222-1224,1263,共4页Journal of Applied Clinical Pediatrics

基　　金：广西自然科学基金(0991117);广西研究生创新计划课题(2009105981002D29)

摘　　要：目的观察布地奈德(BUD)早期干预对哮喘小鼠呼吸道炎症的影响,以及BUD干预对呼吸道IL-6/信号转导与转录激活因子(STAT3)信号通路表达及活化的影响,探讨呼吸道IL-6/STAT3信号通路是否为BUD的作用靶点。方法 40只Balb/c小鼠随机分为正常对照组(n=10)、未干预组(n=10)、BUD干预组(n=10)、AG490干预组(n=10)。卵白蛋白(OVA)致敏制备小鼠哮喘模型,光镜下观察其肺组织结构改变,支气管肺泡灌洗液(BALF)中炎性细胞分类计数,ELISA法检测其BALF中IL-4、IL-5、IL-6水平。Western blot检测各组小鼠肺组织STAT3和磷酸化STAT3(p-STAT3)水平。结果 1.BUD干预组BALF中总细胞数、嗜酸性粒细胞(EOS)计数、EOS%、IL-4、IL-5水平均低于哮喘未干预组(Pa<0.05),与AG490干预组比较差异无统计学意义(P>0.05)。2.BUD干预组BALF中IL-6水平低于哮喘未干预组和AG490干预组,差异均有统计学意义(Pa<0.05)。3.BUD干预组肺组织STAT3和p-STAT3水平均低于哮喘未干预组(Pa<0.05),与AG490干预组p-STAT3水平比较差异无统计学意义(P>0.05)。结论吸入糖皮质激素早期干预可减轻OVA致敏的哮喘小鼠呼吸道炎症,并下调呼吸道IL-6、STAT3的表达和抑制STAT3的活化,呼吸道IL-6/STAT3信号转导通路可能是吸入糖皮质激素防治哮喘的潜在作用靶点之一。Objective To observe the effects of inhaled budesonide （BUD） in early phase on the airway inflammation in asthmatic mouse,and its effects on the IL-6/signal transducers and activators of transcription 3（IL-6/STAT3 ）signaling pathway in airway,explore the therapeutic target of BUD.Methods Forty Balb/c mice were randomly divided into control group（n=10）,asthma group（n=10）,BUD group（n=10） and AG490 group（n=10）.The mice were sensitized with ovalbumin to establish the asthmatic model.The histological changes were evaluated by HE staining.The levels of IL-4,IL-5 and IL-6 in bronchoalveolar lavage fluid （BALF） were measured by enzyme-linked immunosorbent assay.Lung tissue extracts were analyzed for total STAT3 and phospho-STAT3（p-STAT3） by Western blot.Results 1.The levels of inflammatory cells,EOS%, IL-4,IL-5 and IL-6 levels in the BALF in BUD group were significantly lower than those in asthma group （Pa〈0.05）,but,there were no significant difference compared with AG490 group.2.The level of IL-6 in BALF in BUD group was significantly lower than that in asthma group and AG490 group（Pa〈0.05）.3.The levels of total STAT3 and p-STAT3 in the lung in BUD group were significantly lower than those in asthma group （Pa〈0.05）,while the level of p-STAT3 had no significant difference between BUD group and AG490 group （P〉0.05）.Conclusions Inhaled corticosteroid can apparently ameliorate airway inflammation in early phase in asthmatic mouse model,and it can downregulate the expressions of IL-6 and STAT3,inhibit the signal-transduction pathway of STAT3.The IL-6 /STAT3 signaling pathway of airway may be one of the potential therapeutic targets of inhaled corticosteroid.

关 键 词：哮喘 吸入型糖皮质激素 呼吸道炎症 白细胞介素-6 信号转导与转录激活因子3 

分 类 号：R725.6[医药卫生—儿科]