烟雾暴露对支气管哮喘大鼠CCR7和Th1／Th2细胞因子表达的影响  

Effect of cigarette smoke exposure on the expression of CCR7 and levels of Th1/Th2 cytokines inasthmatic rats

作　　者：曹雯 杜永成[1] 李毅[1] 武晓静 张爱珍[1] Cao Wen;Du Yongcheng;Li Yi;Wu Xiaojing;Zhang Aizhen(Department of Respiratory and Critical Care Medicine,Shanxi Provincial People＇s Hospital,Taiyuan 030012,China)

机构地区：[1]山西省人民医院呼吸与危重症医学科,太原030012

出　　处：《中华医学杂志》2018年第28期2264-2268,共5页National Medical Journal of China

基　　金：山西省回国留学人员科研资助项目（2014-重点8）

摘　　要：目的观察烟雾暴露对支气管哮喘（简称哮喘）大鼠肺组织CC趋化因子受体7（CCR7）和辅助性T细胞（Th1/Th2）细胞因子表达的影响。方法40只雄性Wistar大鼠按随机数字表法随机分为对照组、哮喘组、烟雾暴露组和哮喘＋烟雾暴露组各10只。哮喘组用卵清白蛋白（OVA）和氢氧化铝在第1、8天致敏，并于第15天雾化激发，持续8周，对照组以生理盐水代替OVA，烟雾暴露组以生理盐水代替OVA并给予8周香烟烟雾吸入处理，哮喘＋烟雾暴露组每次先给予烟雾吸入再用OVA激发。HE染色观察其肺组织病理变化，免疫组织化学法测定肺组织CCR7表达（以阳性颗粒平均光密度表示），酶联免疫吸附试验（ELISA）检测支气管肺泡灌洗液（BALF）中CC趋化因子配体（CCL）19和CCL21以及血浆中CCL19、CCL21、干扰素（IFN）－γ和白细胞介素（IL）－4的含量变化。结果哮喘组、烟雾暴露组、哮喘＋烟雾暴露组肺组织发生不同程度的炎症反应，其中哮喘＋烟雾暴露组炎症反应最明显；哮喘组、烟雾暴露组、哮喘＋烟雾暴露组肺组织CCR7表达均显著高于对照组（0.350±0.023、0.252±0.022、0.400±0.029比0.180±0.020），哮喘＋烟雾暴露组CCR7表达均显著高于哮喘组和烟雾暴露组（均P〈0.01）；哮喘组、烟雾暴露组、哮喘＋烟雾暴露组BALF和血浆中CCL19和CCL21含量均显著高于对照组，哮喘＋烟雾暴露组CCL19和CCL21含量均显著高于哮喘组和烟雾暴露组（均P〈0.01）；哮喘组、哮喘＋烟雾暴露组大鼠血浆中IFN－γ含量均显著低于对照组[（33±3）、（17±3）比（70±4）pg/ml]，但哮喘＋烟雾暴露组IFN－γ含量低于哮喘组，烟雾暴露组大鼠血浆中IFN－γ含量[（100±5）pg/ml]均显著高于对照组和哮喘＋烟雾暴露组（均P〈0.01）；哮喘组、烟雾暴露组、哮喘＋烟雾暴露组大鼠血浆中IL－4含量均显著高于对照组[（54±4）、ObjectiveTo investigate the effect of cigarette smoke exposure on the expression of CC Chemokine receptor 7 （CCR7） and levels of Th1/Th2 cytokines in asthmatic rats.MethodsForty Wistar rats were randomly divided into four groups： control group, asthma group, smoke exposure group, asthma-smoke exposure group. The asthma group were sensitized with ovalbumin （OVA） and Aluminum hydroxide at day 1, 8 and challenged with OVA at day 15 by atomization for 8 weeks.While control group was sensitized and challenged with normal saline instead of OVA.The smoke exposure group was sensitized and challenged with normal saline instead of OVA followed passive smoking for 8 weeks. The asthma-smoke exposure group was challenged with OVA followed passive smoking. The pathological changes of different groups were observed by HE-staining. CCR7 was semiquantitatively analyzed in lungs by immunohistochemistry.The concentration of CC chemokine ligand （CCL）19, CCL21, interferon （IFN）-γ and interleukin （IL）-4 in peripheral blood and CCL19 and CCL21 in bronchoalveolar lavage fluid （BALF） were measured by enzyme-linked immunosorbent （ELESA） assay.ResultsIn asthma group, smoke exposure group and asthma-smoke exposure group, the various degrees of inflammatory reaction appeared in lung tissue and the asthma-smoke exposure group was with the most significant reaction. In the lung tissues of the rats from asthma group, smoke exposure group and asthma-smoke exposure group, the average optical density （AOD） of CCR7 were significantly higher than those in control group （0.350±0.023, 0.252±0.022, 0.400±0.029 vs 0.180±0.020, all P〈0.01）. The AOD of CCR7 of asthma-smoke exposure group was much higher than both that in asthma group and in smoke exposure group （both P〈0.01）. In asthma group, smoke exposure group and asthma-smoke exposure group, the concentrations of both CCL19 and CCL21 in peripheral blood and BALF were significantly higher than that in control group （all P〈0.01）. The concentration

关 键 词：哮喘 吸烟 受体 趋化因子 T淋巴细胞 辅助诱导 

分 类 号：R562.25[医药卫生—呼吸系统]