中文摘要：

目的：观察抗肝纤维化细胞因子白介素10（IL-10）、肝细胞生长因子（HGF）和干扰素γ（IFN-γ）对含不同-509C〉T基因型的转化生长因子β1（TGF-β1）基因上游启动子转录活性的影响，探讨细胞因子可能的抗肝纤维化机制。方法：以TGF-β1，基因上游5’侧翼区启动子（-1328～＋812）含有-509C〉T位点的片段作为靶序列，将其与氯霉素乙酰基转移酶（CAT）报告基因组成重组体phTGF2．14C、phTGF2．14T，脂质体法转染至人肝癌细胞系HepG2，应用IL-10（4ng／ml）、HGF（10ng／ml）和IFN-γ（20ng／ml）作用于转染后HepG2细胞，ELISA法测定报告基因的表达。结果：转染phTGF2．14C的HepG2细胞报告基因活性明显高于转染phTGF2．14T者（P〈0．01）。IFN-γ对转染phTGF2．14C、phTGF2．14T的HepG2细胞TGF-β1，启动子转录活性均具有明显的抑制作用（P〈0．05），HGF对转染phTGF2．14C HepG2细胞的TGF-β1启动子转录活性具有促进作用（P〈0．05），IL-10对两种情况下HepG2细胞TGF-β1启动子转录活性调控作用均不显著。结论：C等位基因可明显增强TGF—β1基因启动子转录活性；IFN-γ可能通过抑制TGF—β1基因启动子转录活性抑制肝纤维化，而HGF、IL-10的抗纤维化作用可能与此途径无关。

英文摘要：

Objective：To study the regulatory effects of antifibrotic cytokines, interleukin 10 （IL-10）, hepatocyte growth factor （HGF）, and interferon-gamma （IFN-7） on activity of transforming growth factor-β1 （TGF-β1） gene promoter, so as to assess the antifibrotic mechanism of cytokines. Methods： Sequence - 1328-＋812 of TGF-β1 gene, which contains the -509 C〉 T polymorphism, was selected as putative promoter. The recombinant constructions containing -1328-＋ 812 of TGF-β1 gene and CAT reporter gene （phTGF2.14T, phTGF2.14C） were constructed and transfected into HepG2 cells with liposomal trans- fection method, then the transfected HepG2 cells were treated with IL-10 （ 4 ng/ml）, HGF （ 10 ng/ml） or IFN-7（20 ng/ml）. Reporter gene activity was analyzed by ELISA. Results： Reporter gene activity in cells transfected with phTGF2. 14C was sig- nificantly higher than those transfected with phTGF2.14T 〈P〈0.01）. IFN-）＇ significantly inhibited the reporter gene activity in HepG2 cells transfected with phTGF2.14C or phTGF2.14T（P〈0.05）; HGF significantly increased the reporter gene activity in cells transfected with phTGF2.14C （P〈0.05）. IL-10 had no effects on the activities of cells transfected with phTGF2.14C or phTGF2.14T. Conclusion： C allele at -509 can increase the promoter activity of TGF-β1 gene in HepG2 cells. The antifibrotic effect of IFN-7 might be related to its inhibitory effect on the putative promoter activity of TGF-β1 gene; the antifibrotic effects of HGF and IL-10 may not be through regulation of TGF-beta; gene transcription.