抗KL-6抗体减弱博莱霉素诱导的肺纤维化
Bleomycin-induced pulmonary fibrosis is attenuated by anti-KL-6 antibody
徐凌 1杨丹榕 1朱松雷 1顾杰 1丁凤鸣 1边巍 1容朝晖 1沈策1
作者信息
- 1. 200233 上海交通大学附属第六人民医院呼吸科
- 折叠
摘要
目的 探讨抗KL-6抗体对博莱霉素诱导的肺纤维化的预防作用及可能机制.方法 用气管内滴注博莱霉素的方法制作小鼠肺纤维化模型,于滴注博莱霉素前2天开始雾化抗KL-6抗体,至滴注博莱霉素后第21天.通过支气管肺泡灌洗液细胞计数及分类评价肺部炎症情况,通过肺组织病理评分、羟脯氨酸含量评价肺纤维化情况.通过肺组织中KL-6、转化生长因子p1(TGF-β1)、肝细胞生长因子(HGF)水平、Ⅰ型和Ⅲ型胶原的表达及上皮细胞凋亡情况探讨其可能机制.结果 预防性应用抗KL6抗体可显著降低第21天支气管肺泡灌洗液中的细胞总数及巨噬细胞、淋巴细胞数(P＜0.05);降低第14、21天时的肺组织病理评分、羟脯氨酸含量及Ⅰ型、Ⅲ型胶原的表达(P＜0.05);降低各时间点上肺组织中KL-6、TGF-β1水平(P＜0.05);升高第14、21天时HGF水平(P＜0.05);减少各个时间点上的上皮细胞凋亡数(P＜0.05).结论 预防性应用抗KL-6抗体可减弱博莱霉素诱导的炎症和纤维化反应,其治疗效应可能是通过降低Ⅰ型和Ⅲ型胶原的表达、增加HGF的产生、减少KL 6和TGF-β1的产生、降低肺上皮细胞的凋亡而发挥作用.
Abstract
Objective To assess the effect and mechanisms of anti-KL-6 antibody on bleomycininduced pulmonary fibrosis in mice.Methods Pulmonary fibrosis was induced in C57BL/6 mice by intratracheal instillation of bleomycin.Anti-KL-6 antibody was given from two days before bleomycin instillation to the 21st day after bleomycin instillation.Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF) differential cell count.Changes in tissue remodeling were evaluated by quantified pathological examination,measurement of hydroxyproline content.Collagen type Ⅰ and type Ⅲ were detected by qRT-PCR,KL-6,transforming growth factor-β1 (TGF-β1),and hepatocyte growth factor (HGF) in lung tissues were detected by ELISA,and epithelial apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Results Anti-KL-6 antibody significantly reduced the number of alveolar inflammatory cells,macrophages and lymphocytes in BALF on the 21st day after bleomycin instillation (P ＜0.05).On the 14th and 21st day,the histopathological changes of pulmonary fibrosis were attenuated and the increase of lung hydroxyproline content and collagen (type Ⅰ and type Ⅲ) mRNA expression induced by bleomycin were alleviated (P ＜0.05).Moreover,anti-KL 6 antibody down-regulated the increased production of TGF-β1 and KL-6 and up-regulated the decreased production of HGF induced by bleomycin (P ＜0.05).Epithelial apoptosis was also reduced by anti KL-6 antibody (P ＜ 0.05).Conclusions Anti-KL 6 antibody attenuates bleomycin-induced pulmonary fibrosis,possibly through reducing the expression of collagen type Ⅰ and type Ⅲ,increasing HGF level,attenuating the production of KL-6 and TGF-β1,and alleviating epithelial apoptosis.
关键词
肺间质纤维化/KL-6/转化生长因子β1/肝细胞生长因子/凋亡Key words
Pulmonary fibrosis/KL-6/Transforming growth factor β1/Hepatocyte growth factor/Apoptosis引用本文复制引用
基金项目
上海自然科学基金资助项目(10ZR1423100)
出版年
2013
NETL
NSTL
维普
万方数据