Salas Alfonso Leija, Montezuma Tania Díaz, Fariña German Garrido, Reyes-Esparza Jorge, Rodríguez-Fragoso Lourdes
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
Pharmacology. 2008;81(1):41-9. doi: 10.1159/000107968. Epub 2007 Sep 7.
To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats.
Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy.
Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers.
Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease.
评估金雀异黄素对实验性诱导大鼠肝纤维化及基质降解的影响。
通过向大鼠长期给予四氯化碳诱导肝纤维化。为评估金雀异黄素对肝纤维化及肝功能的影响，对肝脏中的总胶原含量和蛋白水解活性进行定量分析。采用免疫组织化学法对实验性纤维化过程中尿激酶型纤溶酶原激活物（uPA）的表达进行定位。使用光学显微镜和电子显微镜评估组织病理学变化。
纤维化且接受金雀异黄素治疗的动物肝脏胶原含量显著降低（73%），肝功能也有所改善（p < 0.001）。金雀异黄素可提高肝纤维化动物肝脏降解I型胶原和基质胶的能力（分别提高3.1倍和3.7倍；p < 0.001）。金雀异黄素增加了uPA免疫反应阳性细胞的数量。uPA表达的增加与蛋白水解活性的增加相关。组织学分析显示中央周围和窦周区域的纤维间隔数量减少。接受金雀异黄素治疗的纤维化动物肝脏的透射电子显微镜图像显示，活化的肝星状细胞数量减少，胶原纤维数量也减少。
金雀异黄素能够改善长期给予四氯化碳诱导损伤和纤维化后的肝脏。这一发现表明金雀异黄素具有抗纤维化潜力，因此可能对治疗慢性肝病有用。
