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Effect of Nitric Oxide on ex vivo normothermic liver perfusion with purely artificial products using artiicial blood.

一氧化氮对使用人工血的纯人工产品离体常温肝脏灌注的影响。

基本信息

批准号：
15591420
负责人：
KATSURAMAKI Tadashi
金额：
$ 2.05万
依托单位：
First Department of Surgery, School of medicine, Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591420/
关键词：
Liver Artificial blood Normothermic perfusion Ischemia reperfusion injury Nitric Oxide Pig

项目摘要

Background. We tried to development of ex vivo hepatic organ culture system, and we have previously demonstrated that development of a normothermic perfusion system that employed artificial products. In this study, we investigated the effects of administration of iNOS inhibitor or NO donor in a normothermic perfusion system with an artificial perfusate using artificial blood.Materials and Methods. A liver graft from a female pig weighting 15 kg was harvested in the usual manner. The Perfusion solution consisted of artificial blood (Neo Red Cell), L-15 medium, distilled water, bovine serum albumin, NaHCO3, NaOH, KC1, human regular insulin, 50% glucose solution, and Hexamethasone. The isolated liver was perfused with this oxygenated perfusate through the portal vein at a rate of 300 ml/min for 6 hours. Selective iNOS inhibitor or NO donor was administration in this perfusion system.Results., Serum contents of AST and LDH level in iNOS inhibitor treatment group markedly dropped and improve oxygen consumption level compared with control group. Histological findings showed that few necrotic areas in 3 hour after perfusion in iNOS inhibitor treatment group compared with control group. NO donor administaration in the perfusion solution improved FischerAfs ratio and decrease cytotoxic amino acid such as serine and methionine. Conclusions. A selective iNOS inhibitor inhibited isolated liver injury. NO donor administration contributed to improvement of amino acid metabolism.

背景我们试图开发离体肝器官培养系统，并且我们先前已经证明了采用人工产品的常温灌注系统的开发。在这项研究中，我们调查的影响，iNOS抑制剂或NO供体的管理在常温灌注系统与人工灌注液使用人造blood.Materials和方法。以常规方式从体重15 kg的雌性猪收获肝移植物。灌注液由人工血（Neo红细胞）、L-15培养基、蒸馏水、牛血清白蛋白、NaHCO 3、NaOH、KCl、人常规胰岛素、50%葡萄糖溶液和地塞米松组成。用该充氧灌注液通过门静脉以300 ml/min的速率灌注离体肝脏6小时。在此灌注系统中给予选择性iNOS抑制剂或NO供体。与对照组相比，iNOS抑制剂治疗组血清AST和LDH水平明显降低，氧耗水平明显改善。组织学检查显示，与对照组相比，iNOS抑制剂治疗组在灌注后3 h内坏死面积较少。灌流液中加入NO供体可提高FischerAfs比率，减少丝氨酸和蛋氨酸等细胞毒性氨基酸。结论.选择性iNOS抑制剂抑制离体肝损伤。NO供体给药有助于氨基酸代谢的改善。