尼可地尔对大鼠供体肺功能和超微结构的影响

The effects of Nicorandil on function and ultrastructure of rat transplanted lung

目的研究钾离子通道开放剂尼可地尔对低温保存后大鼠供体肺功能和超微结构的作用。方法24只健康雄性SD大鼠随机分为3组,A组为常规保存组,EC液灌洗后摘取心肺器官,于4℃恒温冰箱中保存8小时后取出,应用大鼠离体肺灌注模型以5ml/min流量再灌注60分钟;B组为尼可地尔(NCR)组,供体肺灌洗液中含有100μmol/L尼可地尔,余同A组;C组为尼可地尔+格列本脲(NCR+GLY)组,灌洗前15分钟根据体重取1mg/kg量选择性钾离子通道阻断剂格列本脲(Glibenclamide,GLY)经静脉给药,余同B组。再灌注过程中每10分钟测定肺动脉压力(mPAP),每20分钟测定供体肺静脉血氧分压(PvO2),以评定移植肺功能。实验结束时取肺组织观察超微结构改变。结果B组肺mPAP、PvO2及超微结构改变显著优于A组和C组(P<0.05)。A组和C组各项指标无显著性差异(P>0.05),GLY阻断了NCR的有益作用。结论钾离子通道开放剂可改善低温保存后大鼠供体肺功能和超微结构。

Objective To study the effects of potassium channel openers Nicorandil on function and ultrastructure of rat transplanted lung. Methods Twenty-four healthy male SD rats were randomly divided into 3 groups. Group A was control Group, the lungs were flushed with 4℃ modified Euro-Collins solution and preserved for 8 hours, received no Nicorandil; in Group B, the donor lung received Nicorandil （100μmol/L） in the flush solution; In Group C, glibenclamide, a selective adenosine triphosphate-sensitive potassium-channel blocker, was administered 15 minutes before nicorandil administration. Using an isolated, whole blood-perfused, ventilated rat lung model ,Oxygenation, as a surrogate of graft function, was measured using intermittent blood gas analysis of left atrium every 20 minutes during the 60 minutes reperfusion period. The ultrastructure were observed at the conclusion of the reperfusion period. Results Significantly improved arterial oxygenation and uhrastructure were observed in group B compared with group A and C（P〈0.05）. There were no significantly different between the group A and C, which meant Glibenclamide eliminated the beneficial effects of Nicorandil. Conclusion The ATP-sensitive potassium channel openers can improve the function of rat transplanted lung after hypothermic ischemia and storage.