犬急性心肌缺血时循环内皮素和一氧化氮的变化及其相关酶的基因表达

Circulating Endothelin and Nitric Oxide and Myocardial Gene Expression of Relevant Enzymes in Dogs With Acute Myocardial Ischemia

目的：探讨急性心肌缺血犬循环内皮素和一氧化氮的浓度变化以及内皮素转换酶（ＥＣＥ）、一氧化氮合酶（ＮＯＳ）基因在缺血心肌的表达和分布情况。方法：结扎麻醉犬冠状动脉左前降支中段，造成实验性急性心肌缺血模型。采用放射免疫法测定血浆内皮素含量，比色法测定血清一氧化氮代谢产物水平，以原位杂交技术检测缺血心肌中ＥＣＥ和ＮＯＳ信使核糖核酸（ｍＲＮＡ）的表达。结果：随着缺血时间的延长，血中内皮素含量显著升高，而一氧化氮代谢产物水平逐渐下降；缺血３小时后，心肌中ＥＣＥｍＲＮＡ呈高表达，而ＮＯＳｍＲＮＡ呈低表达。结论：心肌缺血时循环内皮素和一氧化氮的浓度变化与ＥＣＥｍＲＮＡ、ＮＯＳｍＲＮＡ表达水平一致，提示内皮素与一氧化氮两者的平衡失调可能参与了心肌缺血性损伤的发生和发展过程。

Objective:The changes of circulating endothelin(ET)and nitric oxide(NO)in acute myocardial ischemic dogs as well as the gene expression of endothelin converting enzyme(ECE)and nitric oxide synthase(NOS) in ischemic myocardium were investigated. Methods:The animal model of acute myocardial ischemia was reproduced in anesthetized dog by ligating the left coronary artery at the middle of anterior descending branch.The plasma ET and serum NO metabolites were determined by radioimmunoassay and colorimetry,respectively.The ECE and NOS gene expressions were observed by in situ hybridization. Results:As the time of occlusion extended,the plasma level of ET elevated significantly to a peak at 120 min after occlusion ( p <0 05),while the serum NO metabolites content gradually decreased( p <0 05).The gene expression of ECE increased and that of NOS decreased in ischemic myocardium 3 hours after the ligation of coronary artery.Thus the changes of circulating ET/NO were consistent with the gene expressions of ECE and NOS in ischemic myocardium. Conclusions:It is suggested that the imbalance between ET and NO may be involved in the occurrence and development of myocardial ischemic injury.