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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。
Objective: To investigate the effect of IFN-γ gene therapy on the expression of transforming growth factor-β1 (TGF-β1) and its receptor in mice infected with Schistosoma japonicum and the anti-hepatic fibrosis effect. Methods: The hepatic cells transfected with the recombinant adenovirus vector of IFN-γ gene were transplanted into mice infected with cercariae of Schistosoma japonicum for 16 weeks. ELISA, immunohistochemistry and dot blot were used to analyze the serum levels of IFN-γ and TGF-β1, and the relationship between the expression of IFN-γ, TGF-β1, TGF-βRII and type Ⅰ and type Ⅲ collagen in mice liver. RESULTS: IFN-γ gene-modified hepatocytes effectively expressed after spleen transplantation and significantly decreased the expression of TGF-β1 and TGF-βRII and the contents of type I and type III collagen. Conclusion: IFN-γ gene therapy can effectively exert anti-schistosomiasis effects on hepatic fibrosis, which may be related to the decrease of TGF-β1 and its receptor.