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

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

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。

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.\;