Mouse model for HBV-associated liver fibrosis
Mouse model for HBV-associated liver fibrosis
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HBV相关肝纤维化小鼠模型
DOI：
10.1055/s-0030-1269459
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发表时间：
2011
影响因子：
1.3
通讯作者：
E Roeb
中科院分区：
文献类型：
--
作者：
Y Churin;M Roderfeld;D Glebe;E Roeb
研究方法：在出生后的不同时间点（3、6和12个月）处死在肝脏中产生HBV大包膜多肽和肝炎B表面抗原（HBsAg）的Tg（C57 BL/6 vs. BALB/c）和它们的非转基因同窝仔。肝细胞损伤程度以血清丙氨酸转氨酶（ALT）活性为指标。肝纤维化的研究，通过不同的方法：天狼星红染色，羟脯氨酸浓度的测量，胶原蛋白的表达，实时PCR和免疫组化estimation.Results：ALT活性较高的Tg在两个遗传背景相比，相应的同窝仔。然而，Tg（BALB/c）显示出比Tg（C57 BL/6）更高的ALT活性，这表明Tg（BALB/c）中的肝损伤更强。肝组织的分析显示，与非转基因小鼠相比，Tg中存在显著的炎症和纤维化。这些观察结果得到了更高的羟脯氨酸含量和激活的胶原蛋白表达在Tg。再次，我们观察到与Tg（C57 BL/6）相比，Tg（BALB/c）中的纤维化更显著。此外，Tg肝脏中α-平滑肌肌动蛋白（SMA）和GFAP的表达升高提示肝星状细胞（HSC）活化。产生HBV包膜多肽的Tg（C57 BL/6和BALB/c）可用作研究HBV相关肝纤维化的模型。2. Tg（BALB/c）似乎比Tg（C57 BL/6）模型更适合于研究纤维化。3. HSC在Tg产生HBV包膜多肽的纤维化发展中起重要作用。
Methods: Tg (C57BL/6 versus BALB/c) producing HBV large envelope polypeptide and hepatitis B surface antigen (HBsAg) in the liver and their non-transgenic littermates were sacrificed at different time points after birth (3, 6 and 12 months). The level of hepatocellular injury was estimated by serum alanine transaminase (ALT) activity. Hepatic fibrosis was studied by different methods: Sirius Red staining, measurement of hydroxyproline concentration, and estimation of collagen expression by real-time PCR and immunohistochemistry.Results: ALT activity was higher in Tg on both genetic backgrounds compared to corresponding littermates. However, Tg (BALB/c) demonstrated more ALT activity compared to Tg (C57BL/6) that suggested stronger liver damage in Tg (BALB/c). Analyses of liver tissue revealed significant inflammation and fibrosis in Tg compared to non-transgenic mice. These observations were supported by higher hydroxylproline content and activation of collagen expression in Tg. Again, we observed a more prominent fibrosis in Tg (BALB/c) compared to Tg (C57BL/6). Further, elevated expression of alpha-smooth muscle actin (SMA) and GFAP in Tg liver suggests hepatic stellate cells (HSC) activation.Conclusions: 1. Tg (C57BL/6 and BALB/c) producing HBV envelope polypeptides can be used as a model for the investigation of HBV-associated liver fibrosis. 2. Tg (BALB/c) seems to be more appropriate to study fibrosis than the Tg (C57BL/6) model. 3. HSCs play an important role in the development of fibrosis in Tg producing HBV envelope polypeptides.