支气管哮喘豚鼠模型支气管肺组织血管细胞粘附分子和Eotaxin的表达及调控  

The expression and regulation of vascular cell adhesion molecules and eotaxin in bronchioles and lung tissue from a guinea-pig model of asthma

作　　者：崔德健[1] 曾泽戎[1] 

机构地区：[1]解放军第三○四医院呼吸科,北京100037

出　　处：《中华结核和呼吸杂志》2002年第11期655-660,I001,共7页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的　研究支气管哮喘 (简称哮喘 )时嗜酸细胞选择性粘附分子———血管细胞粘附分子(VCAM 1)和趋化因子Eotaxin及转录调控因子核因子 (NF) κB、活化蛋白 1(AP 1)在大、小气道及肺组织中的表达 ,探讨嗜酸细胞趋肺的机制。方法　以卵蛋白致敏法制备豚鼠哮喘模型 ,3 6只豚鼠分设 6组 ,每组 6只。对照组 (F组 )、哮喘 1天组 (A组 )、哮喘 4天组 (B组 )、哮喘 14天组 (C组 )、地塞米松注射组 (D组 )、布地奈德吸入组 (E组 )。用免疫组化法分别测定VCAM 1、Eotaxin、NF κB和AP 1在段支气管及细支气管肺泡区的蛋白表达 ,用逆转录 聚合酶链反应 (RT PCR)法测定肺组织匀浆VCAM 1及Eotaxin的mRNA表达 ,电泳迁移实验 (EMSA)测定肺组织匀浆NF κB及AP 1的DNA结合活性。结果各模型组显示 ,与段支气管相似 ,细支气管肺泡区VCAM 1、Eotaxin的蛋白C组分别为 (2 6 3± 3 2、89 0± 8 6)及mRNA相对表达量与F组 (11 2± 3 7、5 0± 4 0 )比较 (P <0 0 1、0 0 0 1) ;NF κB及AP 1的蛋白相对表达量 (C组分别为 179± 7、76± 6) ,与F组 (3 6± 3、2 7± 5 )比较 (P <0 0 1、0 0 0 1) ,且与VCAM 1、Eotaxin呈显著正相关 (r分别 =0 919、0 965　 0 90 4、0 881,P均 <0 0 0 1) ;以上 4项指标在B、C组段支气管及?Objective To evaluate the expression of vascular cell adhesion molecules(VCAM 1) and eotaxin and their transcription factors NF κB and AP 1 in bronchi and bronchioles (with surrounded lung tissue) ,and to investigate the mechanisms for eosinophil chemotaxis to the lungs in a guinea pig model of asthma Methods (1) The guinea pig model of asthma was established by the ovalbumin challenge method (2) The animal models were divided into six groups : control, asthma day 1, asthma day 4, asthma day 14, intraperitoneal dexamethasone, and budesonide inhalation groups (3) The protein expressions of VCAM 1, eotaxin, NF κB and AP 1 in segmental bronchi and in bronchioles and lung tissue were measured by immunohistochemical techniques (4) The mRNA expressions of VCAM 1 and eotaxin in lung tissue homogenates were determined by RT PCR (5) The DNA binding activities of NF κB and AP 1 were measured by electrophoretic mobility shift assay(EMSA) Results (1) In all the asthmatic groups, the protein levels of VCAM 1, eotaxin, NF κB and AP 1, expressed both in central and peripheral airways(26 3±3 2,89 0±8 6,179±7 and 76±6), were significantly elevated compared to those in the control group(11 2±3 7,5 0±4 0,36±3 and 27±5) (2) The mRNA expression levels of VCAM 1 and eotaxin in lung tissue homogenates were significantly higher in the asthmatic groups(2 46±0 38 and 1 080±0 080) than those in the control group(1 05±0 11 and 0 080±0 020) (3) The DNA binding activities of NF κB and AP 1 were significantly increased in the asthmatic groups(256±10 and 78±14), than those in the control group (67±13 and 12±3) (4) All these parameters in both glucocorticoid treated groups were significantly decreased compared to those in the asthma day 14 group, and similar to those in the control group Conclusions VCAM 1 and eotaxin actively participated in the process of eosinophilic inflammation NF κB and AP 1 may play important roles in the regulation

关 键 词：支气管哮喘 豚鼠 支气管肺组织 血管细胞粘附分子 EOTAXIN 表达 调控 

分 类 号：R562.25[医药卫生—呼吸系统]