J4 ›› 2009, Vol. 35 ›› Issue (5): 832-836.

• 基础研究 • 上一篇    下一篇

白细胞介素15在小鼠支气管哮喘发病中的作用

赵凯姝1, 张云峰1, 郭世杰1, 黄艳智2, 高航3, 鲁继荣1   

  1. 1. 吉林大学第一医院儿内一科|吉林 长春130021;2. 吉林省长春市儿童医院ICU科|吉林 长春130061;3. 吉林大学基础医学院病理解剖学教研室|吉林 长春130021
  • 收稿日期:2009-04-15 出版日期:2009-09-28 发布日期:2009-09-28
  • 通讯作者: 张云峰 E-mail:yunfengzhang11@126.com
  • 作者简介:赵凯姝(1972-)|女|吉林省长春市人|副教授|副主任医师|医学博士|主要从事小儿呼吸系统疾病的研究。
  • 基金资助:

    吉林省科技厅科技发展计划项目资助课题(20080444-1);吉林大学第一医院第二届青年发展基金资助课题(200612)

Effect of interleukin-15 in pathogenesis of mouse bronchial asthma

 ZHAO Kai-Shu1, ZHANG Yun-Feng1, GUO Shi-Jie1, HUANG Yan-Zhi2, GAO Hang3, LU Ji-Rong1   

  1. 1.Department of Pediatrics|First Hospital|Jilin University|Changchun 130021|China;2.Changchun Children’s Hospital|Jilin Province|Changchun 130061|China;3.Department of Pathology|School of Basic Medical Sciences|Jilin University|Changchun 130021|China
  • Received:2009-04-15 Online:2009-09-28 Published:2009-09-28

摘要:

目的:通过检测哮喘小鼠血清、肺组织中白细胞介素15(IL-15)的表达,以及与IgE、IL-4、IFN-γ、肺泡灌洗液(BALF)中嗜酸粒细胞(EOS)的关系,探讨IL-15在小鼠支气管哮喘发病中的作用。方法:30只健康雌性BALB C小鼠按完全随机设计原则分为OVA致敏并激发的哮喘模型组(A 组),OVA致敏、激发并予激素治疗组(B组)及正常对照组(C 组)共3组,每组10只。ELISA法检测血清IgE、IL-4、IFN-γ和IL-15的含量;收集BALF行Eos计数;HE染色观察气道炎症及半定量评定炎性细胞浸润程度;免疫组织化学法检测各组小鼠肺组织中IL-15的含量。结果:① 哮喘组小鼠发生行为学改变,肺部组织病理学可观察到明显的 EOS 浸润为主的炎症反应,BALF 中 EOS、血清IgE 和IL-4水平较对照组显著增高(P<0.01),而血清IFN-γ水平较对照组降低(P<0.01),以及IL-4/IFN-γ二者呈负相关关系(r=-0.859,P<0.01),以上均显示哮喘模型制备成功。② 哮喘组小鼠血清IL-15 水平[(77.97±2.75)ng·L-1]高于对照组[(34.63±1.44)ng·L-1](P<0.01);血清IL-15水平与 IgE和IL-4水平均呈正相关关系(r= 0.681,r=0.738,P<0.01),与 IFN-γ 无相关性。③ 哮喘组小鼠肺组织中IL-15的含量高于对照组(P<0.01);哮喘组肺组织中IL-15含量与BALF中EOS呈正相关关系(r= 0.787,P<0.01 )。④ 激素治疗组小鼠肺组织炎症明显减轻、BALF 中的 EOS计数减少、血清IgE水平下降、血清IL-15 的水平及肺组织中IL-15的含量均低于哮喘组(P<0.01)。结论:IL-15在哮喘中可能参与了Th2 类细胞因子IL-4的调节,对于Th1 类细胞因子IFN-γ无明显调节作用。IL-15可能参与了血清IgE水平的调节。IL-15还可能与哮喘 Eos增多有关,进而参与哮喘气道的慢性炎症。糖皮质激素可有效控制哮喘气道炎症。

关键词: 哮喘;疾病模型, 动物;白细胞介素15;Th1/Th2;嗜酸性粒细胞;糖皮质激素

Abstract:

Abstract:Objective To measure the level of interleukin-15 (IL-15) in serum and its expression in lung tissues,and analyze the correlations between IL-15 and IL-4,IFN-γ,eosinophil(Eos),and explore the effect of IL-15 on bronchial asthma.Methods  Thirty femal BALB/C mice were randomly divided into three group (n=10),group A (asthma model),group B (corticosteroid treatment) and group C (normal control).All mice were killed 24 h after final OVA challenge.Blood were obtained for measurement of serum IgE,IL-4,IFN-γ and IL-15 levels by enzyme-linked immunoabsorbent assay (ELISA).Bronchoalveolar lavage fluid (BLAF) was collected for  Eos  count.The left lungs were isolated for pathological examination.The lung sections were stained with hematoxylin and eosin (HE).The expressions of IL-15 in lung tissues were measured by immunohistochemical SP method.Results ① The mouse asthma model appeared ethological changes  specific to asthma,the Eos count in BALF was increased,and IgE and IL-4 levels in serum were also increased compared with control group(P<0.01).The lung tissues also appeared typical pathological changes and the inflammation cell score elevated.The level of serum IFN-γ was decreased(P<0.01).Correlation analysis showed negative relationship between IL-4 and IFN-γ(r=-0.859,P<0.01),there existed Th1/Th2 imbalance.② The level of serum IL-15 in group A (77.97 ng·L-1±2.75 ng·L-1) was higher than that in group C (34.63 ng·L-1±1.44 ng·L-1)(P<0.01).There were positive correlations between the  serum IL-15 and IgE,IL-4 levels(r= 0.681,P<0.01;r= 0.738,P<0.01),while the  serum IL-15 level had no correlation with IFN-γ. ③ The expression of IL-15 in lung tissues in group A was higher than that in group C (P<0.01).There was a positive correlation between the expression of IL-15 in lung tissues and the Eos count in BALF (r= 0.787,P<0.01).④ In mice treated with inhaled budesonide (group B),the Eos count in BALF ,the level of serum IgE ,the level of serum IL-15  and the expression of IL-15 in lung tissues were lower than those in group A(all P<0.01).Conclusion IL-15 might contribute to promoting Th2 cells to secret cytokine IL-4,while not contribute to promoting Th1 cells to secret cytokine IFN-γ.IL-15 might be involved in the elevation of Eos and IgE,which suggests that IL-15 might be involved in the chronic inflammation of bronchial asthma.The inflammation of bronchial asthma could be inhibited by inhaled glucocorticoid.

Key words: asthma;disease models,animal;interleukin-15;Th1/Th2;eosinophil;glucocorticoid

中图分类号: 

  • R725.6