| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
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
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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
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