心肌胰岛素抵抗与心力衰竭大鼠心肌超微结构形态变化的关系

Relationship between myocardial insulin resistance and the myocardial morphological changes in rats with ischemic heart failure

目的探讨心肌胰岛素抵抗对大鼠心肌缺血致心力衰竭的影响。方法雄性Sprague-Dawley(SD)大鼠48只,随机分为对照组(假手术正常心肌)和心力衰竭组,冠状动脉左前降支缝扎术制备大鼠心力衰竭模型。采用超声心动图和心功能分析系统评估大鼠心脏功能。在离体工作心脏灌流模型中,测定葡萄糖和脂肪酸的氧化程度及其在胰岛素刺激下的变化情况。实验结束后取心肌组织观察超微结构并形态学定量测定线粒体损伤程度。结果与对照组比较,心力衰竭组大鼠左心室舒张末期内径增加,而收缩期左心室后壁厚度、心脏射血分数、左心室舒张末期压力、左心室形成压、收缩期和舒张期左心室内压最大变化率明显降低(均P<0.05);胰岛素刺激下,与基础状态下比较,心力衰竭组大鼠葡萄糖氧化量增加率低于对照组[(90±5)%比(229±11)%];脂肪酸氧化量减少率也低于对照组[(47±4)%比(65±3)%,均P<0.05]。心肌细胞超微结构电镜分析显示,心力衰竭组大鼠心肌细胞损伤严重。两组大鼠心肌线粒体损伤程度(Flameng)评分中,心力衰竭组大鼠3、4级心肌线粒体损伤比例显著高于对照组[(76±4)%比(15±7)%,P<0.01]。结论大鼠心力衰竭心肌存在局部的底物氧化水平的胰岛素抵抗,心肌线粒体明显损伤。

Objective To investigate the effect of myocardial insulin resistance on ischemic heart failure of rats.Methods Male Sprague-Dawley（ SD） rats（ n = 48） were randomly divided into two groups： control group and heart failure group,in which rats received the left anterior descending artery（ LAD） ligation to create heart failure models.Echocardiography and cardiac function analysis system were used to evaluate cardiac function. Glucose and fatty acid oxidation rates as well as insulin response were measured in the isolated perfused working heart models. Myocardial morphological changes and degree of mitochondria injury were assessed at the end of the experiment. Results Compared to control group,rats in heart failure group had significantly higher left ventricular end diastolic diameter and lower systolic left ventricular posterior wall thickness,ejection fraction,left ventricular end-diastolic pressure,left ventricular developed pressure and the maximum rate of the change of left ventricular pressure at both systolic and diastolic phase（ all P 〈0. 05）. Under the effect of insulin,the increase of glucose oxidation and the decrease of fatty acid oxidation were both lower in heart failure group [（ 90 ± 5） % vs（ 229 ± 11） % and（ 47 ± 4） % vs（ 65 ± 3） %,respectively,both P 〈0. 05]. Electron microscope study of myocardial morphometric demonstrated that mitochondrial injury was more serious in heart failure group. According to myocardial mitochondria injury severity score（ Flameng）,the percentage of grad 3 or grade 4 injury of myocardial mitochondria in heart failure group was significantly higher than that in control group [（ 76 ± 4） % vs（ 15 ± 7） %,P 〈0. 01]. Conclusion Mitochondria injury and partial insulin resistance at the level of substrate oxidation exist in heartfailure myocardium of rats.