| Project/Area Number |
18591498
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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 |
Digestive surgery
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| Research Institution | Akita University |
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Principal Investigator |
SHIBATA Satoshi Akita University, School of Medicine, Lecturer (40333934)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAWA Hideaki Akita University, School of Medicine, assistant professor (10323148)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,910,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | ischemia reperfusion iniury / gliotoxin / hepatic stellate cells / liver / 外科 / K_<ATP> channel / 細胞保護 |
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| Research Abstract |
Hepatic non-parenchymal cells are attributable to ischemia-reperfusion (I/R) injury of the liver. The contribution of hepatic stellate cells (HSCs) is not well studied. We examined whether the deprivation of HSCs affected the strength of I/R of the liver using gliotoxin that was known to induce apoptosis of HSCs.
The in vivo effect of gliotoxin pretreatment on the liver was examined in the gliotoxin-treated group and non-treated group. Gliotoxin was administered to rats intraperitoneally. The number of HSCs was studied by immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of HSCs. The proportion of GFAP-positive cells to total cells in the liver was evaluated by measuring the stained. Changes in sinusoidal diameter were examined using intravital fluorescence microscopy. Total hepatic ischemia of 30 minutes was induced by Pringle's maneuver and followed by reperfusion of 6 hours. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured to evaluate the I/R injury of the liver in the treated group and the non-treated group.
Gliotoxin treatment significantly decreased the percentage of GFAP-positive cells in the liver. There was no difference in hepatic sinusoidal diameters between the treated and the non-treated groups in zones 1,2 of the liver. However, in zone 3, the sinusoids were wider in the treated group than the non-treated group. Liver damage after I/R was significantly suppressed in the treated group.
Treatment with gliotoxin significantly decreased the number of HSCs in vivo. Pretreatment with gliotoxin prevented I/R injury of the liver. Although a further study is necessary, dilation of the sinusoids in zone 3 might contribute to improving the microcirculation after I/R. It was suggested that HSCs also played a functional role in the I/R injury of the liver and their deprivation might be a novel strategy for ameliorating the liver damage after hepatobiliary surgery.
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