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γ-干扰素基因修饰肝细胞对感染日本血吸虫小鼠TGF-β1及其受体的影响

EFFECTS OF IFN-γ GENE-MODIFIED HEPATOCYTES ON TGF-β1 AND ITS RECEPTOR IN MICE INFECTED WITH SCHISTOSOMA JAPONICUM\+*

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【作者】 张立煌; 姚航平; 曹雪涛; 于益芝; 陈洪; 李敏伟;

【Author】 ZHANG Lihuang\+1, YAO Hangping\+1, CAO Xuetao\+2, YU Yizhi\+2, CHEN Hong\+1, LI Minwei\+11\ The First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003 2\ Department of Immunology, Second Military Medical University, Shanghai 200433

【机构】 浙江大学医学院附属一院传染病研究所!杭州310003; 第二军医大学免疫学教研室!上海200433;

【摘要】 目的: 探讨γ-干扰素 (IFN-γ) 基因治疗对感染日本血吸虫小鼠转化生长因子-β1 (TGF-β1) 及其受体的影响与抗肝纤维化作用的关系。方法: 将小鼠IFN-γ基因重组腺病毒载体转染的肝细胞经脾移植到感染日本血吸虫尾蚴16 wk 的小鼠, 采用ELISA、免疫组化和斑点杂交方法分析小鼠血清IFN-γ与TGF-β1 表达的关系, 小鼠肝内IFN-γ、TGF-β1、TGF-βRII与Ⅰ、Ⅲ型胶原表达的关系。结果: IFN-γ基因修饰的肝细胞经脾移植后能有效地表达, 显著地降低TGF-β1 、TGF-βRII的表达和Ⅰ、Ⅲ型胶原的含量。结论: IFN-γ基因治疗能有效地发挥抗血吸虫病肝纤维化作用, 可能与降低TGF-β1及其受体有关。

【Abstract】 AIM: To explore the anti\|schistosomal hepatic fibrosis effect and the changes in transforming growth factor\|β\-1 (TGF\|β\-1) and its receptors (TGF\|βRII) in S.japonicum infected mice after intrasplenic transplantation of γ\|interferon (IFN\|γ) gene\|modified hepatocytes. METHODS: At 16 wk after infection with cercariae of Schistosoma japonicum, the mice were intrasplenically transplantated with murine hepatocytes which had been transfected with IFN\|γ gene\|combinant adenovirus vector. ELISA, immunohistochemical and dot blot techniques were used to observe the dynamic changes in IFN\|γ, TGF\|β\-1, TGF\|βRII and typeⅠ,Ⅲ collagen. RESULTS: The intrasplenic transplantation of IFN\|γ gene modified hepatocytes effectively expressed IFN\|γ and obviously reduced the production and deposition of typeⅠ,Ⅲ collagen as well as TGF\|β\-1 and TGF\|βRII. CONCLUSION: \{IFN\|γ\} gene transplantation has anti\|hepatic fibrosis efficacy in Schistosoma japonicum\| infected mice, being related to its role of decreasing the expression of TGF\|β\-1 and TGF\|βRII.\;

【基金】 国家自然科学基金!资助项目(No.39730470)
  • 【文献出处】 中国寄生虫学与寄生虫病杂志 ,Chinese Journal of Parasitology and Parasitic Diseases , 编辑部邮箱 ,1999年06期
  • 【分类号】R532.2
  • 【被引频次】17
  • 【下载频次】50
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