State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, China.
Eur J Med Res. 2010 Apr 8;15(4):152-61. doi: 10.1186/2047-783x-15-4-152.
To examine the in vivo anti-fibrotic effect of rat soluble transforming growth factor beta receptor II (RsTbetaRII) and IFN-gamma fusion protein (RsTbRII-IFN-gamma) in rat hepatic fibrosis model.
Model rats were divided into five groups and treated i.m. for 8 weeks: 1) fibrotic model group (each rat, 100 microl of 0.9% NaCl day superset-1); 2) RsTbetaRII-IFN-gamma treatment group (each rat, 0.136 mg x day(-1); 3) IFN-gamma treatment group (each rat, 7.5 MU x day(-1); 4) RsTbetaRII treatment group (each rat, 0.048 mg x day(-1); and 5) mixture of IFN-gamma and RsTbetaRII treatment group (each rat, IFN-gamma 7.5 MU x day(-1)+ RsTbetaRII 0.048 mg x day(-1). After treatment, hepatic fibrogenesis was evaluated by histopathological analysis and measurement of collagen III, alpha-smooth muscle actin (alpha-SMA), TGF-beta1, TGF-betaRII and their mRNA.
Immunohistochemistry, Western blot and real-time RT-PCR showed that RsTbetaRII-IFN-gamma treatment significantly inhibited liver expression of collagen III, alpha-SMA, TGF-beta1 and TGF-betaRII at both protein and mRNA levels. Histopathological analysis also showed that the enhanced anti-fibrotic effects were achieved in model rats treated with RsTbetaRII-IFN-gamma.
Our results confirmed that RsTbetaRII-IFN-gamma has the enhanced effects in reversing hepatic fibrosis.
研究大鼠可溶性转化生长因子β受体Ⅱ(RsTβRⅡ)与 IFN-γ融合蛋白(RsTbRⅡ-IFN-γ)在大鼠肝纤维化模型中的体内抗纤维化作用。
模型大鼠随机分为 5 组,肌肉注射给药 8 周:1)纤维化模型组(每只大鼠,100 μl 0.9%NaCl 日剂量-1);2)RsTbRⅡ-IFN-γ治疗组(每只大鼠,0.136mg·d-1);3)IFN-γ治疗组(每只大鼠,7.5MU·d-1);4)RsTβRⅡ治疗组(每只大鼠,0.048mg·d-1);5)IFN-γ和 RsTβRⅡ混合治疗组(每只大鼠,IFN-γ7.5MU·d-1+RsTβRⅡ0.048mg·d-1)。治疗后,通过组织病理学分析和胶原 III、α-平滑肌肌动蛋白(α-SMA)、TGF-β1、TGF-βRⅡ及其 mRNA 的测量来评估肝纤维化。
免疫组化、Western blot 和实时 RT-PCR 显示,RsTbRⅡ-IFN-γ治疗显著抑制了肝组织中胶原 III、α-SMA、TGF-β1 和 TGF-βRⅡ的蛋白和 mRNA 表达。组织病理学分析也表明,RsTbRⅡ-IFN-γ治疗的模型大鼠的抗纤维化作用增强。
我们的结果证实 RsTbRⅡ-IFN-γ具有增强逆转肝纤维化的作用。