内皮素-1和一氧化氮对家犬肺移植早期缺血-再灌注肺动脉的影响

Effects of endothelin-1 and nitric oxide on ischemia-reperfusion pulmonary arteries in canine lung allotransplantation model

目的 探讨内皮素 (ET) 1和一氧化氮 (NO)对肺移植早期缺血 再灌注 (I/R)损伤的影响及其作用机制。方法 以体重 8.0～ 15 .0kg家犬左肺移植为模型 ,记录肺动脉对ET 1、乙酰胆碱 (Ach)及外源性NO的张力改变并观察ET受体阻断剂及左旋硝基精氨酸 (L NA)的影响。结果 (1)肺动脉对 1× 10 -9mol/LET 1表现出先舒张后收缩的双向反应。 (2 )肺动脉对Ach表现出药量依赖性舒张反应。 (3 )外源性NO对各种肺动脉的舒张反应趋近相同。结论 内皮源性NO在肺移植后I/R损伤中减少而ET 1增多 ,BQ12 3对肺移植早期I/R损伤具有保护作用 。

Objective To study the effects of endothelin (ET) 1 and nitric oxide (NO) on early ischemia reperfusion (I/R) injury in lung allotrasnplantation model and the mechanism. Methods The model of canine left lung allotransplantation model was developed. Isometrical tension responses to ET 1, acetylcholine (Ach) and exogenous NO were recorded in the isolated pulmonary arterial strips pre contracted with prostaglandin F 2a from normal and I/R lungs. The effects of ET receptor antagonist and nitro L arginine were observed. Results ET 1 (1×10 -9 mol/L) induced biphasic responses of transient relaxation followed by constant contraction. Ach (1×10 -9 mol/L to 1×10 -5 mol/L) caused a dose dependent relaxation. Exogenous NO induced similar relaxation in the strips with and without endothelium, L NA treated strips, and the strips from I/R lung. Conclusion Pulmonary arterial endothelia derived NO is markedly reduced during I/R injury after canine lung transplantation, while ET 1 increased. BQ123 had protective and exogenous NO had therapeutic effects on I/R injury after lung transplantation in this model.