中和IL-17A活性改善肺纤维化小鼠肺功能  

Neutralization of IL-17A to Improve Lung Functions of Pulmonary Fibrosis in Mice

作　　者：刘虹[1] 李辙[1] 吕晓希[1] 米粟[1] 

机构地区：[1]北京协和医学院,中国医学科学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《航天医学与医学工程》2013年第1期38-42,共5页Space Medicine & Medical Engineering

基　　金：国家自然科学基金重点项目(81030056);教育部博士点基金(20111106110030)

摘　　要：目的探讨中和细胞因子IL-17A能否改善肺纤维化小鼠的肺功能。方法小鼠随机分为4组,每组30只。假手术组小鼠注射等量磷酸盐缓冲液(phosphate buffered saline,PBS),BLM组气管内注射博来霉素(bleomycin,BLM)造成小鼠急性肺损伤诱导肺纤维化形成。造模后第14天、17天及21天尾静脉注射IL-17A中和性抗体进行治疗(IL-17Ab组),同时注射IgG为对照(IgG组)。造模后第28天,使用Flexivent肺功能检测系统,气管插管检测肺功能。结果中和IL-17A降低BLM导致的动物死亡(P<0.05);降低肺纤维小鼠的胶原沉积(P<0.01)和羟脯氨酸含量(P<0.01);增加肺纤维小鼠的深吸气量(P<0.05);降低气道阻力(P<0.01)和弹性阻力(P<0.01);恢复呼吸系统顺应性(P<0.01)。结论中和IL-17A能改善肺纤维化小鼠的肺功能,为特发性肺纤维化的治疗提供新思路。Objective To investigate if neutralization of IL-17A could improve the lung functions in mouse with pulmonary fibrosis. Methods The mice were divided into 4 groups randomly with 30 in each group. Sham group were injected PBS while BLM group were injected bleomycin （BLM） into the trachea to induce pulmonary fibrosis. Mice injected with BLM were then treated with IL-17A-neutralizing （IL-17Ab group） and IgG antibody （IgG group） on days 14, 17 and 21 respectively. On 28th day after BLM instillation, lung functions were determined by Flexivent. Results Blocking IL-17A with neutralizing antibody increased survival rates of fibrotic animals （P 〈0.05）, decreased the collagen deposition （P 〈0.01 ） and hydroxyproline content in- duced with BLM （ P 〈 0.01 ）, increased inspiratory capacity （ P 〈 0.05 ）, decreased respiratory resistance （ P 〈0.01 ） and elastic resistance （P 〈0.01 ）, augmented static compliance （P 〈0.01 ）. Conclusion Neutral- ization of IL-17A can improve the lung functions in mouse with pulmonary fibrosis. Blocking of IL-17A may be a novel treatment for pulmonary fibrosis.

关 键 词：中和 IL-17A 肺纤维化 肺功能 

分 类 号：R966[医药卫生—药理学]