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Analysis of ischemia-reperfusion injury/primary graft nonfunction of the liver

肝脏缺血再灌注损伤/原发性移植物无功能分析

基本信息

批准号：
07671330
负责人：
SHIMAZU Motohide
金额：
$ 1.34万
依托单位：
KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671330/
关键词：
endothelium leukocyte interaction ischemia-reperfusion of the liver liver transplant PAF IL-1 ICAM-1 in vivo fluorescence imcroscopy PAF拮抗剤生体顕微鏡

项目摘要

A liver ischemia-reperfusion model that was equivalent to liver transplantation was created in male Wistar rats weighing about 200g each, and the role of interleukin 1 (IL-1) and platelet activating factor (PAF) in microcirculatory disorders, especially the interaction between endothelium and leukocytes, was assessed. IL-1 receptor antagonist (IL-Ira) and the PAF receptor antagonist (PAF-A) TCV-309 were infused into the portal vein after 30 minutes of liver ischemia, and the animals were compared with a control group infused with saline. the results showed that administration of IL-Ira and PAF-A mitigated a series of reactions thatoccur after liver ischemia-reperfusion, including ICAM-1 expression on vascular endothelial cells, endothelial-leukocyte interaction, increases in active oxygen, and tissue injury. Thus, IL-1 and PAF were demonstrated to play an important role in the pathogenesis of the tissue injury that occurs after liver ischemia-reperfusion. Next, the effects of IL-1 and … More PAF-A were assessed in a liver transplantation model. Graft preservation was performed for 24 hours with UW solution, and IL-1ra and TCV-309 were used asgraft rinse solution when the graft was collected and before transplantation, with saline being used for rinsing in the control group. There were significantly fewer adherent leukocytes and injured hepatocytes 3 hours after transplantation in the groups given IL-1ra and TCV.In addition, the proportion of sinusoids with flowing blood and leukocyte velocity in the terminal branches of the hepatic vein were significantly higher in the IL-1ra group. The ICAM-1 expression on the endothelium of the sinusoids and central veins observed in the control group was weaker in the TCV group. When post-transplantation survival rates in the control group and the TCV group were compared, the survival rate was found to be significantly greater in the TCV group. Based on the above findings, the microcirculatory injury based on endothelial-leukocyte interaction was demonstrated to be involved in the process of development of cryopreservation-reperfusion injury in liver transplantation. In addition, it appeared that IL-1 and PAF play an important role in the pathogenesis of this injury, and that controlling them would make it possible to maintain graft viability. Less

本研究采用雄性Wistar大鼠建立相当于肝移植的肝脏缺血再灌注模型，观察白细胞介素1（IL-1）和血小板活化因子（PAF）在微循环障碍中的作用，特别是内皮细胞和白细胞之间的相互作用。肝缺血30分钟后，门静脉注入IL-1受体拮抗剂（IL-1 ra）和PAF受体拮抗剂（PAF-A）TCV-309，并与注入生理盐水的对照组进行比较。结果表明，IL-1 ra和PAF-A可减轻肝脏缺血再灌注后的一系列反应，包括血管内皮细胞ICAM-1的表达、内皮细胞与白细胞的相互作用、活性氧的增加和组织损伤。因此，IL-1和PAF被证明在肝脏缺血再灌注后发生的组织损伤的发病机制中起重要作用。接下来，研究IL-1和 ...更多信息在肝移植模型中评估PAF-A。UW液保存移植物24 h，取移植物时及移植前用IL-1 ra和TCV-309冲洗移植物，对照组用生理盐水冲洗。IL-1 ra组和TCV组移植后3 h粘附的白细胞和受损的肝细胞明显减少，IL-1 ra组肝静脉血窦比例和终末支白细胞流速明显增加。对照组肝窦和中央静脉内皮细胞ICAM-1表达较TCV组弱。当比较对照组和TCV组的移植后存活率时，发现TCV组的存活率显著更高。基于上述发现，基于内皮细胞-白细胞相互作用的微循环损伤被证明参与了肝移植冷冻保存-再灌注损伤的发展过程。此外，IL-1和PAF似乎在这种损伤的发病机制中起重要作用，控制它们将使维持移植物活力成为可能。少