2003 Fiscal Year Final Research Report Summary
LIVER PROTECTION AGAINST ISCHEMIAJREPERFUSION INJURY BY ISCHEMIC PRECONDITIONING
| Project/Area Number |
14570452
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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 |
Gastroenterology
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
ARAI Masahiro THE UNIVERSITY OF TOKYO, FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (60271566)
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| Co-Investigator(Kenkyū-buntansha) |
YANASE Mikio THE UNIVERSITY OF TOKYO, DACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (50334397)
TOMIYA Tomoaki THE UNIVERSITY OF TOKYO, FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (90227637)
IKEDA Hitoshi THE UNIVERSITY OF TOKYO, FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (80202422)
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| Project Period (FY) |
2002 – 2003
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| Keywords | ISCHEMIA / REPERFUSION INJURY / ISCHEMIC PRECONDITIONING / LIVER TRANSPLANTATION |
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| Research Abstract |
Brief periods of ischemia followed by reperfusion render tissues resistant against subsequent prolonged ischemia, a phenomenon called ischemic preconditioning. We previously showed that ischemic preconditioning decreased sinusoidal endothelial cell injury and Kupffer cell activation after ischemia/reperfusion with the consequence of improved survival of liver transplant recipients. Although cardioprotective effect of ischemic preconditioning disappears within a few hours, the effect appears again 24-48 hours after ischemic preconditioning, which is called late preconditioning. Since the late preconditioning shows various cardioprotective effects and lasts longer than the early preconditioning, its clinical efficacy is recently drawing attention. Thus we set out to investigate whether late preconditioning works in the liver or not, and to elucidate, if it works, its mechanisms. Ischemia/reperfusion injury was induced in rat livers by clamping hepatic artery and portal vein into the median and left lobes. To evaluate hepatocyte injury, serum activities of ALT and LDH were determined. At first, we decided appropriate ischemic time and the timing of evaluation in the preliminary experiments. Ischemic preconditioning was performed by clamping the hepatic artery and portal vein into the median and left lobes for 10 minutes followed by 10 minutes reperfusion. Ischemic preconditioning reduced liver injury after 60 minutes ischemia and 180 minutes reperfusion. When ischemia/reperfusion injury was induced at 2 hours after ischemic preconditioning, the hepatoprotective effect disappeared. However, ischemia/reperfusion injury induced 24 hours after ischemic preconditioning was reduced compared to no preconditioning group. We are now launching the experiments using adenosine antagonists to investigate the contribution of adenosine receptors to the development of late preconditioning.
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