| Project/Area Number |
12470257
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tokyo Medical and Dental University, Graduate School of Medicine |
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Principal Investigator |
ARII Shigeki Tokyo Medical and Dental Univ., Surgery, Professor, 大学院・医歯学総合研究科, 教授 (50151171)
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| Co-Investigator(Kenkyū-buntansha) |
IMAMURA Masayuki Kyoto Univ., Surgery, Professor, 医学研究科, 教授 (00108995)
KAWAMURA Toru Tokyo Medical and Dental Univ., Surgery, Instructor, 医学部・附属病院, 助手 (90322081)
TERAMOTO Kenichi Tokyo Medical and Dental Univ., Surgery, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80197813)
MORI Akira Kyoto Univ., Surgery, Instructor, 医学研究科, 助手 (60324646)
KAIDOU Toshimi Kyoto Univ., Surgery, Instructor, 医学研究科, 助手 (80314194)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | hepatic sinusoidal cell / cold preservation and reperfusion / hepatochte growth factor / apoptosis / sinusoidal endothelial cell / hepatic stellate cell / Rho / vascular endothelial growth factor / アポト-シス / 肝保存 / 肝移植 / 血管内皮増殖因子 / 肝細胞増殖因子 / 星細胞 |
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| Research Abstract |
1). Cold preservation and reperfusion injury of the liver
Apoptotic change in the liver was studied with Tunel method and electron microscopy in the cold preservation and reperfusion of the rat liver. Consequently, we found that apoptosis was occurred exclusively in the sinusoidal endothelial cells (SECs) with high incidence, leading to the detachment from the sinusoidal wall. This phenomenon was detected markedly in the cold preservation followed by reperfusion, but not in the cold preservation alone. Apoptosis in this experimental model was suppressed by vascular endothelial growth factor (VEGF) which has been well known to function as surviving and proliferative molecule. Furthermore, we showed that SEC of the fatty liver with cold storage was quite fragile and the size of the intra hepatocytic fatty droplet became larger in size as the cold preservation time was longer. These changes in the cold preserved fatty liver appeared to be one of the major causes of non-functioning graft which is frequently occurred in the fatty liver. We demonstrated that hepatocyte growth factor (HGF) ameliorated the impairment of SECs and inhibited enlargement of the fatty droplet. In addition, we showed that expressions of various kinds of the genes were changed during the cold preservation.
2) Improvement of the liver cirrhosis by inhibition of activation of hepatic stellate cells. Previously, we reported that Y-27632, inhibitor of P160ROCK which is an effctor molecule of small G protein Rho, suppressed an activation of hepatic stellate cells, and that this compound inhibited the development into the liver cirrhosis in the CCL4-induced liver fibrosis of the rat. In the present study, we showed that Y-27632 ameliorated the already-established liver cirrhosis in the above-mentioned model without apparent side effects. This result may be a promising strategy for the liver cirrhosis.
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