Molecular analysis of the mechanism of fibrosis in alcoholic liver disease

酒精性肝病纤维化机制的分子分析

• 批准号: 07670624
• 负责人: TSUCHIYA Mariko
• 金额: $ 1.34万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670624/
• 关键词: alcoholic liver disease; liver cirrhosis; nitric oxide; nitric oxide synthase; heme oxygenase; heme oxygenase; 肝線維化; コラーゲン; NOS; エンドトキシン; サイトカイン; hemoxygenase; 肝類洞

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

在酒精性肝损伤纤维化的发病机制中，胶原蛋白可能在其过程中发挥着关键作用。我们在这项研究中假设 IV 型胶原蛋白可能是正弦结构血管生成转化的标志物。然而，在纤维化过程中，I型胶原蛋白占主导地位，很难检测到IV型胶原成分表达的微小变化。使用细胞培养系统来观察IV型胶原蛋白的表达可能是更好的选择。在肝纤维化的另一个方面，一氧化氮（NO）、一氧化碳等多种生物活性物质参与了肝硬化的病理生理过程。这些物质具有与血管活性、细胞因子调节剂和细胞增殖等相关的多个方面，并且推测以不同的方式促进各种病理机制。本研究探讨了几种慢性肝损伤模型中Nox对外内毒素负荷的变化，以及肝脏中一氧化氮合酶（NOS）和血红素加氧酶（HO）mRNA表达的变化。通过给予液体乙醇饮食诱导酒精模型(ALD)，在肝硬化模型中，用硫代乙酰胺治疗大鼠8周。与对照大鼠相比，两种模型中HO-I mRNA均增强，并且Northern分析中肝硬化中的表达更为强烈。脂多糖 (LPS) 刺激 ALD 和肝硬化动物中 mRNA 的 HO-I 表达。至于NOS mRNA表达，两种模型中的eNOS表达均无显着变化，而jNOS虽然不是恒定的，但在Northern和RT-PCR分析中通过LPS处理检测到。结论：1) HO-I mRNA在慢性肝损伤中被诱导，并且通过LPS刺激上调，2)推测NO系统的反应与HO系统相反调节。在慢性肝损伤过程中，生物物质及其合酶根据原发病表现出不同的动态变化。较少的

项目成果

土谷まり子: "慢性アルコール投与ネットの微少循環構築の変化" 日本消化器病学会雑誌. 93. 251 (1996)

Mariko Tsuchiya：“慢性酒精给药网的微循环结构的变化”日本胃肠病学会杂志 93. 251 (1996)。

Mariko Tsuchiya: "The structure of microcirculation in chronic alcoholic rat" Japanese Journal of Gastroenterology. 93. 251

Mariko Tsuchiya：“慢性酒精大鼠的微循环结构”日本胃肠病学杂志。

土谷まり子: "慢性アルコール投与ラットの微小循環構築の変化" 日本消化器病学会雑誌. 93. 251 (1996)

Mariko Tsuchiya：“长期服用酒精的大鼠微循环结构的变化”日本胃肠病学会杂志 93. 251 (1996)。