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

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。

Effects of IFN-gamma gene-modified hepatocytes on TGF-beta 1 and its receptor in mice infected with Schistosoma japonicum]

AIM: To explore the anti-schistosomal hepatic fibrosis effect and the changes in transforming growth factor-beta 1 (TGF-beta 1) and its receptors (TGF-beta RII) in S. japonicum infected mice after intrasplenic transplantation of gamma-interferon (IFN-gamma) 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-gamma gene-combinant adenovirus vector. ELISA, immunohistochemical and dot blot techniques were used to observe the dynamic changes in IFN-gamma, TGF-beta 1, TGF-beta RII and type I, III collagen. RESULTS: The intrasplenic transplantation of IFN-gamma gene modified hepatocytes effectively expressed IFN-gamma and obviously reduced the production and deposition of type I, III collagen as well as TGF-beta 1 and TGF-beta RII. CONCLUSION: IFN-gamma gene transplantation has anti-hepatic fibrosis efficacy in Schistosoma japonicum-infected mice, being related to its role of decreasing the expression of TGF-beta 1 and TGF-beta RII.