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目的探讨γ干扰素(IFNγ)基因修饰的肝细胞经脾移植抗血吸虫病肝纤维化作用。方法采用ELISA和免疫组化方法,动态分析日本血吸虫感染小鼠IFNγ和Ⅰ、Ⅲ型胶原水平及其相互关系,并将小鼠IFNγ重组腺病毒转染的肝细胞经脾移植到感染16周小鼠,分析IFNγ基因治疗血吸虫病肝纤维化的作用。结果感染4周时,小鼠IFNγ水平明显升高,在感染12周时达高峰;但在16周以后IFNγ水平明显下降,而Ⅰ、Ⅲ型胶原的合成持续增高;IFNγ基因修饰的肝细胞经脾移植后能稳定有效地表达,显著降低Ⅰ、Ⅲ型胶原的合成、沉积,减轻肝纤维化程度。结论IFNγ可能与Ⅰ、Ⅲ型胶原的合成、沉积有关;IFNγ基因治疗能有效地发挥抗血吸虫病肝纤维化作用。
Objective To investigate the anti-liver fibrosis effect of interferon-γ (IFNγ) gene modified hepatocyte transplantation on splenic schistosomiasis. Methods ELISA and immunohistochemical methods were used to dynamically analyze the levels of IFNγ and collagen type Ⅰ and Ⅲ in mice infected with Schistosoma japonicum and the correlation between the expression of IFNγ and the collagen type Ⅰ collagen. Infection 16 weeks mice, analysis of IFN γ gene treatment of schistosomiasis liver fibrosis. Results At 4 weeks after infection, the level of IFNγ in mice increased significantly and peaked at 12 weeks of infection. However, the levels of IFNγ decreased significantly after 16 weeks, while the synthesis of type Ⅰ and Ⅲ collagen continued to increase. IFNγ gene modification Of hepatocytes stably and effectively expressed after spleen transplantation, significantly reducing the synthesis and deposition of type I and type III collagen, and reducing the degree of liver fibrosis. Conclusions IFN γ may be related to the synthesis and deposition of type Ⅰ and type Ⅲ collagen. IFN γ gene therapy can effectively inhibit liver fibrosis induced by schistosomiasis.