| Co-Investigator(Kenkyū-buntansha) |
IWATA Kenji Dept.of Surg. Inagi City Hospital, Director, 外科, 医長 (10151739)
SHIRASUGI Nozomu Keio Univerdity School of Medicine, Assistant, 医学部, 助手 (90226324)
SHIMAZU Motohide Keio Univerdity School of Medicine, Assistant, 医学部, 助手 (70124948)
島津 元秀 慶應義塾大学, 医学部, 助手 (80170934)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥12,500,000 (Direct Cost: ¥12,500,000)
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| Research Abstract |
Free radicals are suggested to be one of the most important factors in hepatic ischemia-reperfusion(I/R) injury, and play a major role in primary graft nonfunction after liver transplantation. Cytokines and prostanoids seem to be also important modulators in production of free radicals by target cells, however their relationship is still unclear. First, we investigated the production of free radicals by leukocytes and the microcirculatory changes of the liver after hepatic I/R in rats, using chemiluminescence and in vivo fluolescence microscopy, respectively. And then, we examined the effect of IL-1 receptor antagonist (IL-1ra) and PGE1 in I/R.Second, in liver transplantation model, we studied by the same method as I/R.Results. 1) After I/R, histological examination revealed the liver cell necrosis in no treatment group, but the necrosis was attenuated in IL-1ra group. Free radical production of the blood from suprahepatic vena cava increased compared to infrahepatic vena cava or portal vein in control group, however this increase was suppressed in IL-1ra group. Leukocyte adhesion to the sinusoidal wall was frequetly seen in control group, but in contrast, it was reduced and leukocyte movement was fast and smooth in IL-1ra group. 2) In transplantation , leucocyte velocity and adhesion were correlated with graft survival rate. By rinse and preservation with IL-1ra and PGE1, leucocyte velocity and adhesion, and then graft survival rate were improved. Conclusion. IL-1ra and PGE1 decreased free radical production and microcirculatory disturvances in ischemia-reperfused liver or transplanted liver, and then attenuated the I/R injury or improved the graft survival.
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