结缔组织生长因子单链抗体对博莱霉素诱导的小鼠肺纤维化的影响

Effects of ScFv against CTGF on bleomycin-induced pulmonary fibrosis model

目的:研究结缔组织生长因子(CTGF)单链抗体(ScFv)对博莱霉素诱导的小鼠肺纤维化模型各阶段的支气管肺泡灌洗液(BALF)中炎症细胞数及纤维化程度的影响。方法:昆明小鼠36只,随机分为对照组、模型组和ScFv组,每组12只;后2组麻醉后气管内滴入博莱霉素制备模型,滴药后第2天开始尾静脉分别注入生理盐水或ScFv(4 mg.kg-1),3次.周-1,对照组给予等量的生理盐水;气管内滴药后第7、14、28天分3批处死小鼠,收集左肺BALF,进行炎症细胞计数和分类;肺组织HE染色后观察肺纤维化程度。结果:(1)第7天模型组有明显的肺泡炎,ScFv组小鼠肺泡炎症病变轻微;第28天模型组出现肺纤维化,ScFv组纤维化程度明显低于模型组(P<0.05);(2)第7、14天模型组小鼠BALF中细胞总数及巨噬细胞、淋巴细胞、中性粒细胞均明显高于对照组(P<0.05),ScFv组明显低于模型组(P<0.05)。结论:CTGF ScFv可减少肺纤维化模型BALF中的炎症细胞,减缓肺纤维化的发生发展。

Objective： To investigate the effects of the single-chain variable fragment of antibody（ScFv） against connective tissue growth factor（CTGF） on the inflammatory cells in bronchoalreolar lavage fluid（BALF） and fibrosis dgree of pulmonary fibrosis model induced by bleomycin.Methods： Thirty six male Kunming mice were randomly divided into three groups： the control group,the model group and the ScFv group.The latter two groups were injected with bleomycin via trachea（5 mg·kg-1） and the control injected with saline.Then,the ScFv group were injected ScFv via intravenous（4 mg·kg-1）,and the others were injected saline via intravenous.At the 7th,14th and 28th day after intratrachealed,BALF were collected and pulmonary tissue was used to HE stain.4 mice in each group were sacrificed administration to collect samples,which were used to count and classify cells.The fibrosis degree in the right pulmonary lobe was observed by light microscope.Results：（1） Apparent alveolitis appeared in the model group,while it was much slight in the ScFv group at the 7th day.At the 28th day,both of the groups appeared pulmonary fibrosis,but the fibrosis of ScFv group seemed in a earlier stage（P0.05）.（2） At the 7th and 14th day,the number of cell and the propotion of neutrophils in BALF in the model group were higher than those in the control group（P0.05）.The number of cells and the propotion of neutrophils in BALF in the ScFv group were lower than those in the model group（P0.05）.Conclusion： ScFv can decrease the number of inflammatory cells in BALF of the pulmonary fibrosis model induced by bleomycin,which relieve the airsacculitis of fibrosis of lung.