2001 Fiscal Year Final Research Report Summary
MEASURES AGAINST HEPATIC FAILURE AFTER LIVER TRANSPLANTATION : BASIC INVESTIGATION ON PRECONDITIONING OF THE DONOR LIVER
| Project/Area Number |
12670466
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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 UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (60271566)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Hitoshi The UNIV. OF TOKYO, FACULTY OF MEDICINE, INSTRUCTOR, 医学部・附属病院, 助手 (80202422)
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| Project Period (FY) |
2000 – 2001
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| Keywords | LIVER TRASNPLANTATION / ISCHEMIA REPERFUSION / KUPFFER CELLS / SUPEROXIDE / ADENOSINE / ISCHEMIC PRECONDITIONING |
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| Research Abstract |
When liver is stored and transplanted, sinusoidal endothelial cell injury and activation of Kupffer cells appeared in the early phase of reperfusion, leading to massive hepatic necrosis via microcirculatory disturbance. A brief period of ischemia and reperfusion render tissues resistant against prolonged ischemia, a phenomenon called ischemic preconditioning. We previously reported that ischemic preconditioning decreases sinusoidal endothelial cell injury and Kupffer cell activation, and as the result, improves recipient survival after liver transplantation.In the supported period by the grant, we revealed that l) ischemic preconditioning decreases superoxide production after storage/reperfusion, 2) this effect is reversed by pretreatment with adenosine Al receptor antagonist and 3) liver perfusion with adenosine Al agonist decreases superoxide production after storage/reperfusion like ischemic preconditioning. It is concluded that adenosine released during preconditioning ischemia decreases superoxide production by Kupffer cells after storage/reperfusion via Al receptor pathway. We are at present investigating whether adenosine directly affects Kupffer cells or not using in vitro model.
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