Aller María-Angeles, Arias Jorge-Luis, García-Domínguez Jose, Arias Jose-Ignacio, Durán Manuel, Arias Jaime
Department of Surgery I, School of Medicine, Complutense University of Madrid, Spain.
Fibrogenesis Tissue Repair. 2008 Nov 3;1(1):6. doi: 10.1186/1755-1536-1-6.
Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them.Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis.It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process - although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.
梗阻性胆汁淤积可导致肝硬化和门静脉高压。肝病发展过程中涉及的病理生理机制是多方面且相互关联的。我们建议根据主要在间质空间表达的三种表型对这些机制进行分组，以便将它们整合起来。实验性肝外胆汁淤积是研究梗阻性胆汁淤积最常用的模型。这些实验模型中描述的早期肝脏间质改变会产生具有氧化应激和亚硝化应激的缺血/再灌注表型。然后，库普弗细胞和中性粒细胞参与的白细胞表型过度表达会诱导酶应激。最后，会出现一种血管生成表型，负责胆小管丛的发育和肝血窦动脉化。此外，显著的胆管细胞增殖会获得神经内分泌能力。这一组织病理学发现也与纤维化有关。有人提出，这些炎症表型的序列，或许具有营养意义，最终会产生一个良性肿瘤性胆管病变过程——尽管它会导致严重的肝细胞功能不全。此外，这种良性肿瘤疾病的持续存在会导致更高程度的去分化和自主性，进而导致其恶性变。
