| Project/Area Number |
07457253
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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 |
General surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
DOHI Kiyouhiko School of Medicine, HIROSHIMA UNIVERSITY Professor, 医学部, 教授 (90034024)
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| Co-Investigator(Kenkyū-buntansha) |
MARUBAYASHI Seiji University Medical Hopital, HIROSHIMA UNIVERSITY Assistant Professor, 医学部・附属病院, 講師 (80144814)
ASAHARA Toshimasa School of Medicine, HIROSHIMA UNIVERSITY Asociate Professor, 医学部, 助教授 (70175850)
福田 康彦 広島大学, 医学部, 助教授 (40093801)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | near-infrared spectroscopy / liver ischemia-reperfusion injury / nitric oxide / NM rince / heat shock protein / TNF alpha / FK409 / 生体肝移植 / Kupffer cell blockade / nafamostat mesilate |
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| Research Abstract |
Near-infrared spectroscopy (NIRs) was applied to rat liver for assessing nitric oxide (NO) synthesis and tissue oxygenation as a means of monitoring the rejection response and ischemic injury following liver transplatation. 1. NIRs was performed on the grafts in recipients, and the relative changes in nitrosyl-Hb, oxy-Hb, and oxidized cytochrome oxidase (Cyt.aa_3) were obtained. A significant rise in the level of nitrosyl-Hb was detected from the early phase of acute rejection in the untreated allogeneic group, and the increase was suppessed by deoxy-spergualin treatment. NO synthesis was also increased after long cold preservation in syngeneic liver transplants until day 3. Our NIRs method have a sensitivity to detect NO in the tissues at the level over 10^<-4>M NO,which was analyzed by use of in vivo assay using a spontaneous NO releaser (FK409). Levels of oxy-Hb and oxidized Cyt.aa_3 in the untreated allogeneic group were significantly decreased when parenchymal disorder was confirmed histologically, compared with those in syngeneic group, which remained constant. Thus, our NIRs technique was shown to be capable of assessing simultaneously both the immune resoponse and the degree of immune-induced destruction of graft tissue following liver transplantation through monitoring of NO synthesis and tissue oxygenation. 2. We developed a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor), and NM rinse and Kuppfer cell blockade exert synergistic effect in preventing ischemic injury in cold-preserved liver transplantation. We also reported that livers from fasted rats acquire tolerance to ischemic injury following transplantation. We examined heat shock protein (GRP78, HPS70) and TNF alpha section into the ascitic fluid of fasted rats is markedly suppressed. These findings suggest that induction of cytoprotective substances in the liver may contribute to the tolerance to ischemic injury.
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