Studies on the mechanism and treatment of ischemia-reperfusion injury of the liver
| Project/Area Number |
02454317
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Shimane Medical University |
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Principal Investigator |
NAGASUE Naofumi Assoc. Prof., Surgery II, 医学部, 助教授 (40117198)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Takafumi Assistant, Surgery II, 医学部, 助手 (80243426)
TANIURA Hiroyuki Assistant, Surgery II, 医学部, 助手 (80171833)
CHANG Yu-chung Assistant, Surgery II, 医学部, 助手 (20188501)
KOHNO Hitoshi Lecturer, Surgery II, 医学部, 講師 (60145951)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | liver / transplantation / ischemia-reperfusion / superoxide / calcium / mitochondria / lysosome / cyclosporine / 肝 / 阻血再潅流障害 / ライソゾーム酵素 / クッパー細胞 / 活性酸素 / FK506 / サイクロスポリンA / 肝移植 / 肝阻血 / 再潅流障害 / カルシウムイオン / FKー506 / ケトン体比 |
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| Research Abstract |
Ischemia and reperfusion of the liver are innevitable processes in hepatic transplantation. How are various types of hepatic injury produced by ischemia deteriorate or ameliorate by reperfusion ? This question was studied in terms of intrahepatic calcium level, oxgen derived free radicals and mitochondrial function. In addition, the effects of cyclosporin A and FK506 and Verapamil were investigated in terms of these parameters. The following results were obtained by this study.
(1) Changes in tissue calcium during ischemia and reperfusion of the liver Ca^<2+> in the liver did not change during ischemia but was immediately elevated after reperfusion. The elevated Ca^<2+> was soon expelled from the liver when the ischemic time was short. Upon prolonged ischemia, hepatic Ca^<2+> was reelevated, which was related to the extent of tissue injury and animal death. The release of superoxide did not play a major role in the changes of Ca^<2+> level.
(2) Role of the Kupffer cell in ischemia-reperf
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usion injury of the liver More severe tissue injury was found after ischemia-reperfusion when Kupffer cells were preliminarily activated by zymosan. TNF alpha and beta were not involved in the process, but increased production of superoxide seemed to play an important role.
(3) Plasma activities of lysosomal enzymes in porcine liver transplantation After liver grafting in pigs, plasma activities of beta-galactosidase, beta-glucosidase and beta-glucuronidase increased with their peaks at 3 hours, which returned to normal within 2 to 3 days. These changes reflected the severity of liver injury well.
(4) Effects of cyclosporin A and FK506 on ischemia-reperfusion injury of the liver Pretreatment with these two drugs showed a protective effect on ischemia-reperfusion injury of the canine and porcine livers. The effect seemed to be mediated through lysosomal stabilization and protection of mitochondrial morphology and function.
(5) Effect of Verapamil on prolonged liver ischemia and reperfusion Despite numerous works reporting the beneficial effect of Verapamil on liver ischemia, this drug was not effective on 180 minute warm ischemia, showing that the effect of Verapamil differs according to the ischemic time. Less
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Report
(4 results)
Research Products
(28 results)
