CpG ODN对小鼠哮喘模型气道高反应性及炎症影响的研究  

Effect of CpG ODN on airway hyperresponsiveness and inflammation in mouse asthma model

作　　者：肖建军[1] 李孟荣[2] 郭伟[3] 李昌崇[2] 黄敏[4] 

机构地区：[1]温州医学院附属第三医院儿科,瑞安325200 [2]温州医学院附属育英儿童医院呼吸内科 [3]天津市儿童医院呼吸内科 [4]温州医学院生物医学工程系

出　　处：《浙江医学》2011年第11期1575-1579,共5页Zhejiang Medical Journal

基　　金：温州市科技局对外科技合作交流项目（H20090021）

摘　　要：目的探讨免疫刺激序列CpG寡聚脱氧核苷酸（ODN）对小鼠哮喘模型气道高反应性（AHR）及炎症过程的影响。方法雌性C57BL／6J小鼠30只，随机分为正常对照组（A组）、模型组（B组）、CpGODN预防组（C组）、CpGODN治疗组（D组）及布地奈德治疗组（E组），建立小鼠哮喘模型。采用有创体积描记法对小鼠进行肺功能及AHR检测；采集血、肺组织及支气管肺泡灌洗液（BALF）标本，对BALF行细胞总数计数及嗜酸粒细胞（EOS）绝对值计数，ELISA法测定血清和BALF中细胞因子IL一4、IFN—γ水平。结果B组BALF中细胞总数、EOS绝对值计数和EOS占细胞总数的百分比（EOS％）均显著高于A组（均P〈001），C、D、E组均显著低于B组（均P〈0．01），但仍显著高于A组（P〈0．05或0．01）。B组气道阻力增加幅度（Raw％）和肺顺应性下降幅度（Cdyn％）均显著高于A组（P〈0．01）；C、D、E组较B组显著降低（均P〈0．01）；C、D、E组肺组织炎症程度改变不一，明显比B组减轻。B组血清和BALF中IL-4的水平显著高于A组（P〈0．01），而BALF中IFN—γ的水平显著低于A组（P〈0．01）。结论CpGODN在致敏阶段及致敏后均能明显改善哮喘肺组织炎症，降低BALF中细胞总数及EOS％；降低AHR；调节Th1/Th2细胞因子的平衡。致敏后CpGODN干预优于致敏阶段的干预。Objective To investigate the effect of immunostimulatory DNA sequence CpG ODN on airway hyperresponsiveness （AHR） and inflammation in mouse asthma model. Methods Thirty female C57BL/6J mice were randomized into five groups （6 in each）： control group （A）, model group （B）, CpG ODN prevention group （C）, CpG ODN treatment group （D） and budesonide treatment group （E）. Asthma was induced in mice of groups B, C, D, F and E. The lung function and AHR were evaluated with plethysmography, blood, BALF, and lung tissue samples were collected. The total cell numbers and the numbers of EOS were counted; and the concentrations of IL-4 and IFN-γ in serum and BALF were measured by ELISA. Results The total cells numbers, the absolute numbers of EOS, the ratio of EOS to the total cells numbers （EOS%） of group B were significantly higher than those of group A （P 〈 0.01）; Those indexes in groups C, D and E were significantly lower than those in group B （P 〈 0.01）, while higher than those in group A（P 〈 0.05 or 0.01）. The incremental amplitude of Raw（Raw%） and descendent amplitude of Cdyn（Cdyn%） in group B were significantly higher than those in group A （P〈 0.01）, while those indexes in groups C, D and E were significantly lower compared with group B（P〈 0.01）. The pathological inflammatory changes were also found in groups C, D and E, but were much milder than those in group B. The serum and BALF IL-4 concentration in group B was significantly higher than that in group A （P〈 0.01）, but the BALF concentration of IFN-γ in group B was significantly lower than that in group A （P〈 0.01）. Conclusion CpG ODN can improve pulmonary inflammation and suppress AHR in mouse asthma model; and it is more effective when administrated after sensitization than in sensitizing period.

关 键 词：哮喘 CPG寡聚脱氧核苷酸 小鼠 气道高反应性 体积描记法 

分 类 号：R587.102[医药卫生—内分泌]