丁基苯酞在大鼠心肌急性梗死过程中保护效应

发布时间：2018-01-31 21:41

本文关键词： 丁基苯肽冠状动脉结扎线粒体损伤细胞凋亡凋亡指数心肌梗死　出处：《安徽医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：研究背景和目的NBP在急性脑卒中过程中，具有提高大脑能量代谢，抗氧化作用，促进微循环，减少神经细胞凋亡以及抑制炎症反应的作用。NBP同样被证明可减少内皮细胞缺氧诱导的线粒体活性氧(Reactive oxygen species ROS)的形成，减轻由急性缺氧导致的超氧化物歧化酶(superoxide dismutase, SOD)的活性的降低，减少线粒体损伤以及线粒体膜电荷的损失，保护线粒体结构和功能的完整性，进而降低神经细胞网凋亡和急性脑卒中引起的大脑梗死面积。所以本将观察丁基苯酞对大鼠心肌梗死后对心肌细胞线粒体，心肌梗死面积及心肌细胞凋亡的作用。研究方法共64只雄性SD大鼠，分为假手术组8只，模型组、实验组各28只。用大豆油溶解丁苯酞液体（将丁苯酞稀释在食用油大豆油制成8mg/ml的丁苯酞溶液备用，按80mg/kg灌胃），实验组对大鼠灌胃丁苯酞溶液，其余两组均只灌胃大豆油，每日2次，每次1ml/100g。以上各组灌胃饲养一周后制备心肌梗死模型。其中模型组和实验组需通过结扎冠状动脉左前降支建立MI模型，假手术组仅开胸，未结扎冠状动脉。模型组和实验组分别于结扎冠脉后1h、4h、8h和12h取心脏标本，，每个时间点7只大鼠。TUNEL法检测实验大鼠AMI过程梗死交界区心肌细胞凋亡。各组取心肌组织应用TTC染色分析心肌梗死面积，电子透射显微镜观察4h后各组梗死交界区的心肌细胞的超微结构，根据样本线粒体的损伤程度，评估整体线粒体得分。Western-bloting法检测大鼠心肌梗死4h后Bcl-2、Bax的蛋白含量，计算Bcl-2/Bax的比值。研究结果与模型组相比，在大鼠急性心肌缺血过程中，丁基苯肽可有效抑制线粒体损伤；同时急性心肌梗死后12h丁基苯酞可显著减少大鼠急性心肌梗死面积(P0.05)；丁苯酞可显著减少心肌细胞凋亡(P0.05)。丁苯酞可明显改善线粒体损伤丁基苯肽显著提高Bcl-2蛋白表达水平及Bcl-2/Bax的比值。研究结论丁基苯肽可显著提高Bcl-2蛋白表达水平及Bcl-2/Bax的比值，减少线粒体损伤，降低心肌梗死过程中细胞凋亡指数，缩小心肌梗死面积，具有显著地心肌保护效应。
[Abstract]:Background and objective NBP plays an important role in improving brain energy metabolism, antioxidant activity and microcirculation during acute stroke. NBP has also been shown to reduce mitochondrial reactive oxygen species (Ros) induced by hypoxia in endothelial cells. The formation of Reactive oxygen species ROS. It can reduce the activity of superoxide dismutase (SOD) induced by acute hypoxia, and reduce the damage of mitochondria and the loss of membrane charge. Protect the integrity of mitochondria structure and function, and then reduce apoptosis of neural network and cerebral infarction area caused by acute cerebral apoplexy. Therefore, we will observe the effect of Ding Ji phthalide on myocardial mitochondria after myocardial infarction in rats. The effect of myocardial infarction area and cardiomyocyte apoptosis. Methods 64 male SD rats were divided into sham-operated group (n = 8) and model group (n = 8). The experimental group (n = 28) was dissolved in butadiphthalein liquid with soybean oil (8mg / ml butylphthalide solution was prepared by dilution of butylphthalide in edible oil soybean oil, and was perfused by stomach at 80 mg / kg). The rats in the experimental group were given butyphthalide solution, and the other two groups were only given soybean oil twice a day. Myocardial infarction model was established in each group of 1 ml / 100 g. The model group and experimental group need to establish MI model by ligating the left anterior descending coronary artery, and the sham operation group only opened the chest. No coronary artery was ligated. The heart samples were taken from the model group and the experimental group at 1 hour after coronary artery ligation for 8 h and 12 h, respectively. Tunel method was used to detect myocardial cell apoptosis in the infarct junctional area of experimental rats during AMI at each time point. Myocardial tissue was taken from each group to analyze myocardial infarction area by TTC staining. Electron transmission microscope was used to observe the ultrastructure of myocardial cells in each group after 4 hours, according to the damage degree of mitochondria. The total mitochondrial score. Western-blotting method was used to detect the protein content of Bcl-2P Bax and calculate the ratio of Bcl-2/Bax in rats with myocardial infarction 4 h after myocardial infarction. Results compared with the model group, Ding Ji benzopeptide could effectively inhibit mitochondrial damage during acute myocardial ischemia in rats. At the same time, 12h after acute myocardial infarction, Ding Ji phthalide could significantly reduce the area of acute myocardial infarction (AMI) in rats (P 0.05). Butyphthalide could significantly reduce cardiomyocyte apoptosis (P 0.05). Butyphthalide could significantly improve the expression level of Bcl-2 protein and the ratio of Bcl-2/Bax to Bcl-2/Bax after mitochondrial injury of Ding Ji. Conclusion Ding Ji benzopeptide can significantly increase the expression level of Bcl-2 protein and the ratio of Bcl-2/Bax, reduce mitochondrial damage and decrease apoptosis index during myocardial infarction. Reducing myocardial infarction size has significant myocardial protective effect.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R542.22

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