CAJ | 학술논문

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.
목적 탐토항KL-6항체대박래매소유도적폐섬유화적예방작용급가능궤제.방법 용기관내적주박래매소적방법제작소서폐섬유화모형,우적주박래매소전2천개시무화항KL-6항체,지적주박래매소후제21천.통과지기관폐포관세액세포계수급분류평개폐부염증정황,통과폐조직병리평분、간포안산함량평개폐섬유화정황.통과폐조직중KL-6、전화생장인자p1(TGF-β1)、간세포생장인자(HGF)수평、Ⅰ형화Ⅲ형효원적표체급상피세포조망정황탐토기가능궤제.결과 예방성응용항KL6항체가현저강저제21천지기관폐포관세액중적세포총수급거서세포、림파세포수(P＜0.05);강저제14、21천시적폐조직병리평분、간포안산함량급Ⅰ형、Ⅲ형효원적표체(P＜0.05);강저각시간점상폐조직중KL-6、TGF-β1수평(P＜0.05);승고제14、21천시HGF수평(P＜0.05);감소각개시간점상적상피세포조망수(P＜0.05).결론 예방성응용항KL-6항체가감약박래매소유도적염증화섬유화반응,기치료효응가능시통과강저Ⅰ형화Ⅲ형효원적표체、증가HGF적산생、감소KL 6화TGF-β1적산생、강저폐상피세포적조망이발휘작용.
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.