Tsukamoto H, Matsuoka M, French S W
Department of Internal Medicine, VA Medical Center, Martinez, California.
Semin Liver Dis. 1990 Feb;10(1):56-65. doi: 10.1055/s-2008-1040457.
No experimental model reproduces exactly human liver fibrosis by etiology. Nonetheless, each of the models reviewed in this article has served to enhance our understanding of pathogenetic mechanisms of liver fibrosis. There have been important common findings derived from several different models. The best example is the role of Ito cells in liver fibrogenesis. Involvement of Ito cells was consistently seen in the experimental models regardless of whether the fibrogenic stimulus was nutritional, hepatotoxic, or immunologic. Cellular and molecular mechanisms of Ito cell activation have begun to be explored in different models. Another example is the role of TGF beta in liver fibrogenesis. In both murine schistosomiasis model and Tsukamoto-French rat model, TGF beta was shown to be closely associated with fibrogenesis. With both in vitro and in vivo experimental approaches using cellular and molecular techniques, the experimental model of liver fibrosis will continue to provide data on the pathogenetic mechanisms of liver fibrogenesis. Future genetic and molecular approaches may allow development animal models with liver fibrosis that is inducible and genetically similarity to that of man.
没有任何实验模型能完全按照病因复制人类肝纤维化。尽管如此,本文所综述的每种模型都有助于增进我们对肝纤维化发病机制的理解。从几种不同模型中已经得出了重要的共同发现。最好的例子是肝星状细胞在肝纤维化形成中的作用。无论致纤维化刺激是营养性的、肝毒性的还是免疫性的,在实验模型中始终能看到肝星状细胞的参与。在不同模型中已经开始探索肝星状细胞激活的细胞和分子机制。另一个例子是转化生长因子β在肝纤维化形成中的作用。在小鼠血吸虫病模型和冢本-弗伦奇大鼠模型中,转化生长因子β都被证明与纤维化形成密切相关。通过使用细胞和分子技术的体外和体内实验方法,肝纤维化实验模型将继续提供有关肝纤维化发病机制的数据。未来的基因和分子方法可能会使诱导性且在基因上与人类相似的肝纤维化动物模型得以开发。