目的 探讨大黄素对心肌梗死后心力衰竭大鼠心肌细胞能量代谢的作用及其对细胞外信号调节激酶（extra-cellular signal regulated kinase，ERK）信号的调节机制。 方法 采用结扎左前降支的方法构建大鼠心肌梗死模型，将动物模型按照随机数字表法分为模型组、低剂量组、中剂量组、高剂量组以及对照组，每组10只；同时另取10只大鼠作为假手术组，假手术组动物在造模术中只进行穿线，不结扎；低剂量组、中剂量组、高剂量组大鼠每日分别以20、40、60 mg/kg大黄素灌胃，对照组以10 mg/kg卡托普利灌胃处理，连续给药14 d，统计分析各组大鼠的左室射血分数（left ventricular ejection fraction，LVEF）、左室收缩期末内径（left ventricular end-systolic diameter，LVESD）、左室舒张期末内径（left ventricular end-diastolic diameter，LVEDD）、室间隔厚度（interventricular septum thickness，IVS）等心功能的变化，TUNEL染色检测大鼠心肌细胞凋亡率，JC-1染色法检测大鼠心肌细胞线粒体膜电位，Western blot检测心肌组织中线粒体呼吸链复合物Ⅰ（complex Ⅰ）蛋白和p-ERK的表达。 结果 与假手术组相比，模型组，低、中、高剂量组和对照组大鼠的LVEDD、LVESD、心肌细胞凋亡率以及心肌组织中complex Ⅰ和p-ERK的表达均明显升高，LVEF、IVS、心肌细胞线粒体膜电位明显降低，差异均具有统计学意义（P<0.05）；与模型组相比，低、中、高剂量组和对照组大鼠的LVEDD、LVESD、心肌细胞凋亡率以及心肌组织中complex Ⅰ和p-ERK的表达均明显降低，IVS、LVEF、心肌细胞线粒体膜电位明显升高，差异均具有统计学意义（P<0.05）；并且这些观察指标的变化均具有明显的大黄素剂量依赖性（P<0.05）。 结论 大黄素能明显改善心肌梗死后心力衰竭大鼠的线粒体损伤以及能量代谢，降低心肌组织细胞凋亡率，改善心功能。
Abstract
Objective To investigate the effects of emodin on the energy metabolism of cardiomyocytes in rats with heart failure after myocardial infarction and its regulation mechanism on extra-cellular signal regulated kinase (ERK) signaling pathway. Methods The left anterior descending branch was ligated to construct a rat model of myocardial infarction. Successfully modeled animals were randomly divided into a model group, a low-dose group, a middle-dose group, a high-dose group and a control group according to the random number table method, each with 10 animals; at the same time, another 10 rats were taken as a sham operation group. Animals in the sham operation group were only threaded, but not ligated; rats in the low-dose group, middle-dose group, and high-dose group were treated with 20 mg/kg, 40 mg/kg, 60 mg/kg emodin by gavage every day. The rats in the control group were treated with captopril at 10 mg/kg. After 14 days of continuous administration, the left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), and ventricular septal thickness(IVS) of each group of rats were statistically analyzed. TUNEL staining was used to detect the apoptosis rate of rat cardiomyocytes. JC-1 staining was used to detect the mitochondrial membrane potential of rat cardiomyocytes. Western blot was used to detect the expressions of mitochondrial respiratory chain complex Ⅰ(complex Ⅰ) protein and p-ERK in myocardial tissue. Results Compared with the sham operation group, the LVEDD, LVESD, myocardial cell apoptosis rate, and the expression of complex I and p-ERK in myocardial tissue were significantly increased in the model group, low, medium, high dose group and the control group. LVEF, IVS and the mitochondrial membrane potential of cardiomyocytes were significantly reduced, and the differences were statistically significant (all P<0.05). Compared with the modern group, the LVEDD, LVESD, myocardial cell apoptosis rate, and the expression of complex I and p-ERK in myocardial tissue were significantly reduced in the low, medium, high dose group and the control group. LVEF, IVS and the mitochondrial membrane potential of cardiomyocytes were increased significantly, and the differences were statistically significant (all P<0.05). Conclusions Emodin can significantly improve the mitochondrial damage and energy metabolism in heart failure rats after myocardial infarction, reduce the apoptosis rate of myocardial tissue, and improve the cardiac function of experimental animals.
关键词
大黄素 /
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心肌梗死 /
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心力衰竭 /
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能量代谢 /
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细胞外信号调节激酶信号
Key words
Emodin /
Myocardial infarction /
Heart failure /
Energy metabolism /
Extra-cellular signal regulated kinase signaling pathway
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基金
四川省留学归国人员科研启动基金（20160032）
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