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程度及羟脯氨酸含量的影响  

The effect of ScFv against CTGF on bleomycin-induced pulmonary fibrosis of mice and hydroxyproline content

作　　者：刘朝朝[1] 王西华[2] 吴国球[3] 苟丽霞[1] 

机构地区：[1]东南大学临床医学院,江苏南京210009 [2]东南大学附属中大医院呼吸科,江苏南京210009 [3]东南大学附属中大医院临床检验中心,江苏南京210009

出　　处：《东南大学学报（医学版）》2010年第2期135-138,共4页Journal of Southeast University(Medical Science Edition)

基　　金：国家自然科学基金资助项目(30970809)

摘　　要：目的:研究结缔组织生长因子(CTGF)单链抗体(ScFv)对博莱霉素诱导的肺纤维化小鼠的治疗作用。方法:昆明小鼠36只,随机分为对照组、模型组和治疗组,每组12只;对照组气管内滴入生理盐水,模型组和治疗组气管内滴入博莱霉素(5 mg.kg-1)制备肺纤维化模型。第2天开始治疗组尾静脉注射ScFv(4 mg.kg-1),对照组和模型组给予等量的生理盐水(约100μl.次-1),3次.周-1。第14、28天分两批处理动物,用HE染色行病理组织学检查并进行纤维化分级,用酸水解法测定肺组织羟脯氨酸的含量。结果:对照组小鼠肺组织无纤维化形成;模型组肺组织可见肺泡破坏,肺泡间隔大量纤维化,肺组织中羟脯氨酸含量及纤维化程度较对照组明显增高(P<0.01)。治疗组肺组织纤维化程度较模型组明显减轻,且羟脯氨酸含量较模型组显著降低(P<0.01)。结论:ScFv作为CTGF单链抗体可明显减轻纤维化程度,有可能成为治疗肺纤维化一种新的药物。Objective： To investigate therapeutic effect of single-chain variable fragment（ScFv） against connective tissue grouth factor（CTGF） on bleomycin-induced pulmonary fibrosis of Kunming mice.Methods： 36 Kunming mice were randomly divided into three groups： the control group,the model group and the treatment group,12 rats in each group.Mice in the control group were injected with normal saline via trachea,mice in the model and treatment group were injected with bleomycin（5 mg·kg-1） via trachea for preparing models.Then,mice the treatment group were injected with ScFv（4 mg·kg-1） via intravenous,and the mice in the other groups were injected with normal saline（about 100 μl·time-1）via intravenous,3 times·week-1.After be modeled 14 and 28 days,dealing with animals by hematoxylin-eosin staining for histopathological examination and fibrosis grade,by acid hydrolysis for assaying lung hydroxyproline content.Results： There was no pulmonary fibrosis in the control group;in the model group,a large number of alveolus damaged,alveolar septum fibrosis,hydroxyproline content and fibrosis were significantly higher than that in the control group（P0.01）;in the treatment group,lung fibrosis was significantly alleviated and the content of hydroxyproline was significantly lower than that in the model group（P0.01）.Conclusion： ScFv against CTGF can delay the fibrosis,which may become a new cure for pulmonary fibrosis.

关 键 词：结缔组织生长因子单链抗体 羟脯氨酸 肺纤维化 小鼠 

分 类 号：R563[医药卫生—呼吸系统] R33-33[医药卫生—内科学]