2001 Fiscal Year Final Research Report Summary
Effects of neuroendocrine factors on the exaggeration of liver injury: Study using ex vivo and in vitro system
| Project/Area Number |
12670496
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Ehime University |
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Principal Investigator |
IWAI Masaru Ehime University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00184854)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Masatsugu Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (40150338)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Liver injury / Necrosis / Apoptosis / Sympathetic nervous system / Catecholamine / Hepatic sinusoidal cell / Cytokines |
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| Research Abstract |
The present study was designed to explore the mechanism of the action of hepatic sympathetic nerves on aggravation of liver injury. Using ex vivo system with perfused rat liver, and in vitro system with cultured hepatocytes, we have had the new findings as follows:
1) In perfused rat liver after treatment with galactosamine, the electrical stimulation of hepatic sympathetic nerve increased the leakage of LDH and AST from the liver. Similar changes were observed not only by the infusion of catecholamine, ATP but also by the factors secreted from sinusoidal cells like endothelin, suggesting that the effects of hepatic sympathetic nerves were at least partly by hepatic sinusoidal cells. 2) Because not only necrosis but also apoptosis was observed in galacttfsamine-induced liver injury, we examined the involvement of cytokines which induce apoptosis. In perfused rat liver after treatment with galactosamine, hepatic nerve stimulation increased the secretion of TNF and IL-6 from the liver. The increased secretion of TNF and IL-6 was observed in regenerating liver after partial hepatectomy, indicating that the cytokines may stimulate liver regeneration. Since the release of TNF and IL-6 was significantly inhibited by pretreatment of rat with gadolinium, these cytokines were produced by sinusoidal cells. 3) Cultured hepatocytes and non-parenchymal cells isolated from rat liver showed cell death by galactosamine in the cultured medium in a dose-dependent manner. The cell death induced by galactosamine increased by the addition of noradrenaline or ATP in the medium. The co-culture of hepatic parenchymal cells and non-parenchymal cells showed similar changes. These results suggested the aggravation of liver injury induced by hepatic nerve stimulation was regulated by the complicated mechanism including hepatic sinusoidal cells.
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Research Products
(24 results)
