摘要
目的 探讨吗啡预处理的晚期心肌保护作用以及诱导型一氧化氮合酶 (iNOS)在此过程中的作用。方法 建立在体小鼠冠状动脉阻断的心肌缺血再灌注模型。吗啡预处理 2 4h后 ,小鼠心肌缺血 4 5min ,再灌注 12 0min。用氯化三苯四唑 ( 2 ,3,5 triphenyltetrazoliumchloride ,TTC)染色确定梗死心肌范围。心肌梗死范围以梗死心肌 (IS)占缺血区心肌 (AAR)的重量百分比表示。并观察选择性iNOS抑制剂 (S methylthioureasulfate ,SMT)和iNOS基因敲除对吗啡预处理心肌保护作用的影响。结果 缺血再灌注后野生对照组IS/AAR为 4 3%± 5 % ,2 4h前给予吗啡可以使IS/AAR显著降低至 2 2 %± 4 % (P <0 0 5 )。吗啡预处理后再给予SMT可以取消吗啡的心肌保护作用。吗啡预处理对iNOS基因敲除小鼠完全没有心肌保护作用。结论 吗啡预处理具有晚期心肌保护作用。
Objective To explore the late cardioprotection induced by morphine preconditioning and determine the role of inducible nitric oxide synthase(iNOS) in mediating this effect Methods Thirty two wild type (WT) mice and 16 iNOS gene knockout mice, totally 48 mice, underwent ligation of the left anterior descending coronary artery (LAD) for 45 minutes and reperfusion for 120 minutes The 32 wild type mice were randomly divided into 4 groups of 8 mice: WT control group, 24 hours before the heart occlusion, normal saline was given; WT+morphine group, 24 hours before the heart occlusion morphine was administered; WT+SMT group, 24 hours before the heart occlusion normal saline was administered and 30 minutes before heart occlusion S methylthiourea sulfate (SMT), a selective inhibitor of iNOS, was administered; and WT+morphine+SMT group, 24 hours before the heart occlusion morphine was administered and 30 minutes before heart occlusion SMT was administered The 16 iNOS gene knockout mice were randomly divided into 2 groups of 8 mice: iNOS (-/-) control group (24 hours before the heart occlusion normal saline was given) and iNOS (-/-)+morphine group (24 hours before heart occlusion. morphine was administered) One hundred and twenty minutes after reperfusion, the LAD was re ligated at the original site for all the mice Evans blue was injected via right carotid artery catheterization to stain the non ischemic area of the heart Then the hearts of all mice were taken out, cut into 5 pieces with similar thickness, and put into the solution of 2,3,5 triphenyltetrazolium chloride (TTC) The heart was fixed in formalin solution, underwent digital photography, and weighed NIH Image software was used to calculate the area of the left ventricle (LV), infarct size (IS), and area at risk (AAR) The size of myocardial ischemia was expressed as AAR/LV, and the scope of myocardial infarction was expressed as IS/AAR Results The IS/AAR of the WT control group was 43%±5%, significantly larger than that of the WT+mor
出处
《中华医学杂志》
CAS
CSCD
北大核心
2004年第11期891-895,共5页
National Medical Journal of China
