Improvement of outcome after fatty liver transplantation
| Project/Area Number |
13671229
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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 |
General surgery
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| Research Institution | Osaka Medical College |
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Principal Investigator |
HAYASHI Michihiro Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 講師 (90314179)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Koichi Kyoto University, Graduate school, Professor, 医学研究者, 教授(大阪医科大学客員教授) (20115877)
TANIGAWA Nobuhiko Osaka Medical College, Faculty of Medicine, Professor, 医学部, 教授 (00111956)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | liver transplantation / fatty liver / Hepatocyte Growth Factor(HGF) / choline-methionine-deficient diet / apoptosis / liver regeneration / preservation-reperfusion injury / cold presrvation / 肝移植 / 実験的脂肪肝 / グラフトviability / HGF / 脂肪肝グラフト |
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| Research Abstract |
Transplantation of livers with severe steatosis may result, in primary nonfunction of the grafts. Protective strategies are very rare to safely expand the donor pool to fatty liver. Hepatocyte Growth Factor (HGF) is known as the most potent mitogen for hepatocytes and has been shown to have protective effect and stimulate regeneration in injured livers. Here we examined the effects of human recombinant HGF (hrHGF) on function and survival of preserved fatty liver transplantation. Fatty livers obtained from choline-methionine-deficient diet -fed rats were orthotopically transplanted in normal rats after 12-hour cold preservation. In the HGF group, donor rats were pretreated with hrHGF, and hrHGF was also added to the preservation solution. Twelve hours after hrHGF injection, lipid analyses demonstrated increased serum levels of triglyceride, total cholesterol, low density lipoprotein and very low density lipoprotein. Recipient rat survival was significantly increased in hrHGF-pretreated group compared with control. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels in the effluent before graft revascularization and serum ALT, LDH and HA at 2 hour after reperfusion were significantly low in FLGF group, accompanied with increased hyaluronic acid uptake rate. Pretreatment with hrHGF also significantly reduced the TUNEL positive cells and increased BrdU positive hepatocytes at 2 hour after reperfusion. Sinusoidal endothelial cells (SECs) damage and hepatocyte apoptosis were more severe in control group observed by transmission electron microscope. In conclusion, hrHGF has both protective effects on hepatocytes and SECs at fatty liver transplantation. It inhibited apoptosis of fatty liver during preservation reperfusion injury and induced graft regeneration at early stage after transplantation. Also it might lead to recovery of steatosis by increasing secretion of lipids out of liver.
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Report
(4 results)
Research Products
(1 results)
