1996 Fiscal Year Final Research Report Summary
Analysis of ischemia-reperfusion injury/primary graft nonfunction of the liver
| Project/Area Number |
07671330
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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 | KEIO UNIVERSITY |
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Principal Investigator |
SHIMAZU Motohide KEIO UNIV.SCHOOL OF MED.ASSIST.PROFESSOR, 医学部, 講師 (70124948)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Minoru KEIO UNIV.SCHOOL OF MED.ASSISTANT, 医学部, 助手 (50197513)
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| Project Period (FY) |
1995 – 1996
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| Keywords | endothelium / leukocyte interaction / ischemia-reperfusion of the liver / liver transplant / PAF / IL-1 / ICAM-1 / in vivo fluorescence imcroscopy |
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| Research Abstract |
A liver ischemia-reperfusion model that was equivalent to liver transplantation was created in male Wistar rats weighing about 200g each, and the role of interleukin 1 (IL-1) and platelet activating factor (PAF) in microcirculatory disorders, especially the interaction between endothelium and leukocytes, was assessed. IL-1 receptor antagonist (IL-Ira) and the PAF receptor antagonist (PAF-A) TCV-309 were infused into the portal vein after 30 minutes of liver ischemia, and the animals were compared with a control group infused with saline. the results showed that administration of IL-Ira and PAF-A mitigated a series of reactions thatoccur after liver ischemia-reperfusion, including ICAM-1 expression on vascular endothelial cells, endothelial-leukocyte interaction, increases in active oxygen, and tissue injury. Thus, IL-1 and PAF were demonstrated to play an important role in the pathogenesis of the tissue injury that occurs after liver ischemia-reperfusion. Next, the effects of IL-1 and
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PAF-A were assessed in a liver transplantation model. Graft preservation was performed for 24 hours with UW solution, and IL-1ra and TCV-309 were used asgraft rinse solution when the graft was collected and before transplantation, with saline being used for rinsing in the control group. There were significantly fewer adherent leukocytes and injured hepatocytes 3 hours after transplantation in the groups given IL-1ra and TCV.In addition, the proportion of sinusoids with flowing blood and leukocyte velocity in the terminal branches of the hepatic vein were significantly higher in the IL-1ra group. The ICAM-1 expression on the endothelium of the sinusoids and central veins observed in the control group was weaker in the TCV group. When post-transplantation survival rates in the control group and the TCV group were compared, the survival rate was found to be significantly greater in the TCV group. Based on the above findings, the microcirculatory injury based on endothelial-leukocyte interaction was demonstrated to be involved in the process of development of cryopreservation-reperfusion injury in liver transplantation. In addition, it appeared that IL-1 and PAF play an important role in the pathogenesis of this injury, and that controlling them would make it possible to maintain graft viability. Less
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[Publications] Shito, M., Wakabayashi, G., Ueda, M., Shimazu, M., et al: "Interleukin-1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion injury inthe rat." Transplantation. 63. 143-148 (1996)
Description
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