Molecular analysis of the mechanism of fibrosis in alcoholic liver disease

在酒精性肝损伤纤维化的发病机制中，胶原可能起着关键作用。我们在这项研究中假设IV型胶原可能是窦状隙结构血管生成转化的标志物。但在肝纤维化过程中，I型胶原的变化占主导地位，IV型胶原的微小变化很难检测到，用细胞培养系统观察IV型胶原的表达可能是较好的方法。一氧化碳参与肝硬化的病理生理学。这些物质具有与血管活性、血管紧张素调节剂和细胞增殖等有关的多个方面，并被推测以不同的方式促成各种病理机制。本研究观察了外源性内毒素负荷时Nox的变化，以及Nox mRNA表达的变化。 关于我们 观察了几种慢性肝损伤模型肝组织中一氧化氮合酶（NOS）和血红素氧合酶（HO）的变化。酒精中毒模型（ALD）用酒精饲料诱导，酒精中毒模型用硫代乙酰胺治疗8周。北方分析显示，两种模型大鼠肝组织HO-Ⅰ mRNA表达均较对照组增强，且肝硬化组HO-Ⅰ mRNA表达更强。脂多糖（LPS）刺激ALD和酒精中毒动物HO-1 mRNA表达。结论：1）慢性肝损伤时HO-Ⅰ mRNA表达上调，LPS刺激后NO系统对HO系统的反应可能是反调节的。在慢性肝损伤过程中，生物物质及其合成酶随原发病的不同而呈现不同的动态变化。少

In the pathogenesis of fibrosis in alcoholic liver injury, collagen may play a critical role in its process. We hypothesized in this study that type IV collagen might be a marker of angiogenetic transformation of sinusoidal structure. However, type I collagen dominantly changed in the fibrotic process, it was difficult to detect the small change of the expression of type IV collagen component.It may be preferable to use the cell culture system for the observation of the expression of type IV collagen.In another aspect of liver fibrosis, several biological active substances, such as, nitric oxide (NO), carbon monoxide are involved in the pathophysiology of liver cirrhosis. These substances have multiple aspects relating to vasoactivity, cytokine-modulator and cell-proliferation etc., and are speculated to be contributing to various pathological mechanisms in a different manner. In this study, we investigated the changes of Nox on the loading of external endotoxin, and the mRNA expressio … More n of nitric oxide synthase (NOS) and heme oxygenase (HO) in the liver in several models of chronic liver injury. Alcoholic model (ALD) was induced by the administration of a liquid ethanol diet, and in cirrhotic model, rat was treated with thioacetamide for 8 weeks. HO-I mRNA was enhanced in both models comparing with control rat, and the expression was more intense in cirrhosis in the Northern analysis. Lipopolysaccharide (LPS) stimulated the HO-I expression of mRNA in ALD and cirrhotic animals. As to NOS mRNA expression, there were no significant changes in eNOS expression in both models, and jNOS was , not constantly, but detected in Northern and RT-PCR analysis, by LPS treatment.Conclusion : 1) HO-I mRNA was induced in chronic liver injury, and was up-regulated by LPS stimulation, 2) the response of NO system was speculated to be counter-regulated toward HO system. In the process of chronic liver injury, biological substances and their synthase show different dynamics dependent of the primary disease. Less