中国寄生虫学与寄生虫病杂志 ›› 1999, Vol. 17 ›› Issue (6): 3-333.

• 论著 • 上一篇    下一篇

γ-干扰素基因修饰肝细胞对感染日本血吸虫小鼠TGF-β_1及其受体的影响

张立煌1;姚航平1;曹雪涛2;于益芝2;陈洪1;李敏伟1
  

  1. 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
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:1999-12-30 发布日期:1999-12-30

EFFECTS OF IFN-γ GENE-MODIFIED HEPATOCYTES ON TGF-β_1 AND ITS RECEPTOR IN MICE INFECTED WITH SCHISTOSOMA JAPONICUM*

ZHANG Lihuang1;YAO Hangping1;CAO Xuetao2;YU Yizhi2;CHEN Hong1;LI Minwei1

  

  1. 1\ The First Affiliated Hospital;Medical College of Zhejiang University;Hangzhou 310003 2\ Department of Immunology;Second Military Medical University;Shanghai 200433
  • Received:1900-01-01 Revised:1900-01-01 Online:1999-12-30 Published:1999-12-30

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。

关键词: γ-干扰素, 基因治疗, 血吸虫病, 转化生长因子-β_1, 转化生长因子-β受体

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.\;

Key words: interferon, gene therapy, schistosomiasis, transforming growth factor-β\-1, transforming growth factor receptorII