Effects of Na+/H+ exchanger inhibitor to ischemic-reperfusion injury in non-heart beating pancrea graft

Na/H交换抑制剂对无心跳胰腺移植缺血再灌注损伤的影响

• 批准号: 13671211
• 负责人: FUJIMORI Keisei
• 金额: $ 2.62万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671211/
• 关键词: ischemic reperfusion injury; pancreas transplantation; NHE exchanger inhibitor; pig pancreas allotransplantation; rat pancreas reperfusion model; islet; 膵ラ島; 阻血再灌流障害; H+ポンプ阻害薬; Ca拮抗薬; ブタ膵移植; 心停止ドナー; 細胞内カルシウム; アラキドン酸代謝産物; 再灌流障害

In pHi recovery after the NH4C1 prepulse technique in Wister rat pancreatic islets, FR183998 showed an effect of a potent Na+/H+ exchanger inhibitor. An inhibition of intracellular Ca2+ overload was not evaluated in Fura-2 fluorescence signals. FR effects In the tail segment of rat ischemic models, the FR were not evaluated from pancreatic duct injury. In more than 90 min. of the whole pancreas ischemia, administration of FR before ischemia ameliorates edema after reperfusion. The pancreatic tissue PO2 with LICOX after reperfusion, FR group showed high PO2 value in more than 90 min. ischemia, though there is not statistically significant. Pigs (20-25kg) are used as the pancreatic allotransplantation model. Pancreas grafts are retrieved from non-heart beating donors after 60 minutes periods of cardiac arrest. Grafts were preserved in the UW solution at 4°C for 24 hours. Blood glucose, IRI, s-and u-amylase was examined at every postoperative day. IVGTT test was performed at 7 POD. Graft ATP measurement and histological examination was performed. FR iv injection and perfusion of the UW solution added FR ameliorated interstitial edema. Graft survival rate in the FR group, which graft is administered FR before 60 minutes normothermic ischemia and stored 24 hours in UW solution added FR, was significantly higher than in the non-FR group. In conclusion, it was suggested that Na+/H+ exchanger inhibitor, FR 183998, improves normothermic and hypothermic ischemia-reperfusion injury to some extent, though a relationship with intracellular Ca2+ concentration could not be revealed.

在Wister大鼠胰岛中NH 4C 1预脉冲技术后的pHi恢复中，FR 183998显示出强效Na+/H+交换抑制剂的作用。在Fura-2荧光信号中未评价细胞内Ca 2+过载的抑制。FR效应在大鼠缺血模型的尾段中，未从胰管损伤评估FR。在全胰腺缺血超过90分钟时，缺血前给予FR可改善再灌注后的水肿。再灌注后胰腺组织PO 2与LICOX比较，FR组在缺血90 min以上显示较高的PO 2值，但无统计学意义。猪（20- 25 kg）用作胰腺同种异体移植模型。胰腺移植物在心脏骤停60分钟后从无心脏跳动的供体中取出。将移植物在4°C下在UW溶液中保存24小时。术后每天检测血糖、IRI、s-淀粉酶和u-淀粉酶。在POD 7时进行IVGTT试验。进行移植物ATP测定和组织学检查。静脉注射FR和灌注加FR的UW液可减轻间质水肿。在常温缺血60分钟前给予FR并在UW液中保存24小时的FR组移植物存活率显著高于非FR组。结论：Na+/H+交换抑制剂FR 183998对常温和低温缺血再灌注损伤有一定的保护作用，但与细胞内Ca ~（2+）浓度的关系尚不明确。