中和白细胞介素17对博来霉素诱导小鼠肺纤维化的干预作用  

Protective effect of neutralizing interleukin-17 on Bleomycin-induced pulmonary fibrosis in mice

作　　者：宋桂芹[1] 马立飞 赵铁军[2] 张效云[1] Gui-qin Song;Li-fei Ma;Tie-jun Zhao;Xiao-yun Zhang(Department of Biochemistry,HeBei North University,Zhangjiakou,Hebei 075000,China;Life Science Center,HeBei North University,Zhangjiakou,Hebei 075000,China)

机构地区：[1]河北北方学院生物化学教研室,河北张家口075000 [2]河北北方学院生命科学中心,河北张家口075000

出　　处：《中国现代医学杂志》2019年第3期1-7,共7页China Journal of Modern Medicine

基　　金：河北省高等学校科学研究项目(No:ZD2017206);河北省张家口市科学技术研究与发展计划项目(No:1821029D);河北省高等学校科学技术研究项目(No:Z2018250)

摘　　要：目的初步探讨中和白细胞介素17(IL-17)对博来霉素(BLM)诱导小鼠肺纤维化形成过程的干预作用及其机制。方法 96只小鼠随机分为4组,即抗体干预组、同型抗体对照组(IgG2A组)、博来霉素组(BLM组)、正常对照组(NC组)。气管内注射BLM使小鼠急性肺损伤诱导肺纤维化形成,NC组则给予等量生理盐水。复制模型后第4、9、14、19和22天抗体干预组小鼠尾静脉注射IL-17A中和抗体,IgG2A组注射同型抗体IgG2A;BLM组和NC组则注射等量生理盐水。在培养的第7、14和28天将4组小鼠分批处死,取气管肺泡灌洗液(BALF)涂片进行细胞计数,ELISA法检测IL-1β、IL-10、IL-17A、IFN-γ含量的变化;检测小鼠肺组织羟脯氨酸(HYP)、丙二醛(MDA)及活性氧(ROS)等生化指标,并评价各组小鼠肺组织的纤维化程度。结果抗体干预组与BLM组比较,BALF中细胞总数、淋巴细胞、单核细胞、中性粒细胞的个数,IL-1β、IL-10、IFN-γ的含量,以及HYP、MDA、ROS的含量在各个时间点均降低(P <0.05);而IgG2A组上述指标在各个时间点与BLM组比较,差异无统计学意义(P>0.05)。结论中和IL-17A对BLM所致的实验性小鼠肺纤维化模型具有一定的防治作用,有利于延缓肺纤维化的进程。Objective To explore protective effect of neutralizing Interleukin-17(IL-17) on Bleomycin(BLM)-induced pulmonary fibrosis in mice.Methods Totally 96 mice were randomly divided into antibody intervention group(antibody group),IgG group,BLM group and control group(n = 24).Endotracheal injection of BLM was performed resulting in acute lung injury and pulmonary fibrosis in mice.Mice in control group received normal saline.Mice were treated with IL-17 neutralizing antibody,IgG2 A or BLM at day 4,9,14,19,22 in antibody group,IgG2 A group and BLM group,respectively.Mice were sacrificed 7,14,21,28 days,after cell culture,bronchoalveolar lavage fluid(BALF) was used to detect cell count.IL-1 β,IL-10,IL-17 A and IFN-γ were measured by Elisa kits.Hydroxyprine(HYP),malonaldehyde(MDA) and reactive oxygen species(ROS) in lung tissue were determined.Histological characterization of pulmonary fibrosis was evaluated.Results Number of lymph,monocytes,neutrophils,concentration of IL-1β,IL-10,IFN-γ,IL-17 A,and expression of HYP,MDA and ROS were decreasedsignificantly in antibody group when compared with those in BLM group(P<0.05).No obvious differences in the mentioned indexes were witnessed between IgG group and BLM group(P >0.05).Conclusions Blockage of cytokine IL-17 A effectively reduces BLM induced pulmonary fibrosis in mice through mediating inflammatory response.

关 键 词：肺纤维化 博来霉素 白细胞介素17 小鼠 

分 类 号：R563[医药卫生—呼吸系统] R34[医药卫生—内科学]