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

在Wistar大鼠胰岛NH4Cl预脉冲技术后PHI的恢复中，FR183998显示了一种有效的Na+/H+交换抑制剂的作用。在Fura-2荧光信号中未发现对细胞内钙超载的抑制作用。在大鼠缺血模型的尾段，FR的作用没有从胰管损伤的角度进行评估。在超过90分钟内。在全胰腺缺血时，缺血前给予FR可减轻再灌流后的水肿。LICOX组再灌流后胰腺组织PO2值明显升高，FR组90min以上PO2值明显升高。缺血，虽然没有统计学意义。选用体重20~25 kg的猪作为同种异体胰腺移植模型。胰腺移植物在心脏骤停60分钟后从非心脏跳动的供者那里取回。移植物在4℃的UW液中保存24小时。术后每一天检测血糖、胰岛素抵抗指数、S和U-淀粉酶。在7d时进行IVGTT试验。进行移植物三磷酸腺苷测定和组织学检查。FR静脉注射加加FR的UW液灌流可减轻间质水肿。移植物在常温缺血60min前给予FR，并在含FR的UW液中保存24小时后，移植物存活率显著高于非FR组。以上结果提示，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程度的改善作用，但与细胞内钙离子浓度的关系不明显。

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.