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

以体重约200g的雄性Wistar大鼠为实验对象，建立相当于肝移植的肝缺血再灌注模型，观察白细胞介素1 （IL-1）和血小板活化因子（PAF）在微循环疾病中的作用，特别是内皮细胞与白细胞的相互作用。肝缺血30min后，将IL-1受体拮抗剂（IL-Ira）和PAF受体拮抗剂（PAF- a） TCV-309输注门静脉，与输注生理盐水的对照组进行比较。结果显示，IL-Ira和PAF-A可减轻肝脏缺血再灌注后发生的一系列反应，包括血管内皮细胞上ICAM-1的表达、内皮-白细胞相互作用、活性氧增加和组织损伤。因此，IL-1和PAF在肝脏缺血再灌注后组织损伤的发病机制中发挥了重要作用。下一步，在肝移植模型中评估IL-1和PAF-A的作用。移植物用UW溶液保存24小时，采集移植物时和移植前用IL-1ra和TCV-309作为移植物冲洗液，对照组用生理盐水冲洗。移植后3小时，IL-1ra组和TCV组的粘附白细胞和损伤肝细胞明显减少。此外，IL-1ra组肝静脉终末支血流窦的比例和白细胞速度均显著升高。对照组大鼠鼻窦和中心静脉内皮细胞ICAM-1表达较TCV组弱。比较对照组和TCV组的移植后生存率，发现TCV组的生存率明显高于对照组。综上所述，以内皮-白细胞相互作用为基础的微循环损伤参与了肝移植低温保存-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

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