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Reperfusion Injury of the Liver and Stomach in Liver Transplant

肝移植中肝胃再灌注损伤

基本信息

批准号：
04404053
负责人：
KITAJIMA Masaki
金额：
$ 9.28万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404053/
关键词：
Hepatic ischemia-reperfusion Liver transplantation Free radical Cytokine Microcirculation Primary graft nonfunction IL-1 receptor antagonist Prostagrandin E1 肝阻血・再灌流 Primary Graft Nonfunction Prostograndin E1 IL-1receptor antagonist

项目摘要

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.

自由基是肝脏缺血再灌注损伤的重要因素之一，在肝移植术后移植物失功能中起重要作用。细胞因子和前列腺素类似乎也是靶细胞产生自由基的重要调节剂，但它们之间的关系仍不清楚。首先，我们研究了白细胞的自由基的产生和肝脏的微循环变化后，肝I/R大鼠，分别使用化学发光和在体荧光显微镜。在肝移植模型中，采用与I/R相同的方法，观察IL-1受体拮抗剂（IL-1 ra）和前列腺素E1（PGE 1）对I/R的影响。1)I/R后，组织学检查未治疗组肝细胞坏死，IL-1 ra治疗组肝细胞坏死减轻。对照组肝上腔静脉血自由基生成量高于肝下腔静脉或门静脉血，IL-1 ra组肝上腔静脉血自由基生成量低于肝下腔静脉或门静脉血。对照组可见较多白细胞粘附于窦壁，而IL-1 ra组白细胞粘附减少，白细胞运动迅速、平稳。2)在移植中，白细胞速度和粘附与移植物存活率相关。采用IL-1 ra和PGE 1冲洗和保存，可提高白细胞流动速度和粘附能力，从而提高移植物存活率。结论IL-1 ra和PGE 1可减少缺血再灌注肝和移植肝的自由基产生和微循环障碍，从而减轻I/R损伤或提高移植肝存活率。