压力超负荷早期大鼠心脏心肌细胞自噬变化的时程研究

发布时间：2018-02-20 00:03

本文关键词： 压力超负荷心肌肥厚心肌细胞自噬时程变化　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:心肌细胞自噬在维持正常心脏结构和功能中起重要作用。我们和其他前期研究表明,在小鼠压力超负荷诱导心肌肥厚和心力衰竭模型上,在心力衰竭期,心肌细自噬明显增加,增加的心肌细胞自噬与心肌细胞凋亡和心功能降低有关。然而,在压力超负荷诱导心肌肥厚早期,心肌细胞自噬的变化尚未完全阐明。本研究在腹主动脉缩窄诱导压力超负荷大鼠模型上探究心肌细胞自噬的时程变化及其与心肌肥厚的关系。方法:1.动物实验造模:体重180-200g雄性SD大鼠行腹主动脉缩窄术(Abdominal aorta constriction,AAC),并设立假手术sham组,造模成功后分别于术后1h,3h,6h,24h,48h,72h处死。2.实验分组:(1)AAC组30只,分别于术后1h,3h,6h,24h,48h,72h不同时间点处死5只;(2)假手术组(sham)10只,分别于术后6h,72h各处死5只。3.心肌肥厚和心肌细胞自噬指标测定:心脏重量和体重比率(HW/BW,心脏重量指数),左心室重量和体重比率(LVW/BW,左心室重量指数)用于评估心肌肥厚;HE染色观察心肌细胞大小的改变;应用Western blot技术检测心肌组织自噬相关蛋白的表达。结果:AAC术后AAC 1h和3h时,与假手术相比,心脏重量和左心室重量指数没有明显变化,AAC术后6h,HW/BW比率有轻度增加趋势。AAC术后24h时,HW/BW比率,LVW/BW比率有进一步增加趋势,48h和72h时显著增加。AAC组72h与假手术sham组相比有统计学意义。HE染色显示72h AAC组心肌细胞直径较Sham组增大,细胞排列杂乱;免疫印迹结果表明,与假手术组相比,AAC组,心肌细胞自噬指标LC3II/I比率,Beclin1和Atg12蛋白表达显著降低。结论:压力超负荷早期大鼠心脏心肌细胞自噬进行性降低,心肌细胞自噬降低与心肌肥厚有关。提示在压力超负荷诱导心肌肥厚早期,应用心肌细胞自噬诱导剂可能有益于心肌肥厚的预防和治疗。
[Abstract]:Objective: myocardial autophagy plays an important role in maintaining normal cardiac structure and function. Myocardial fine autophagy was significantly increased, and increased myocardial autophagy was associated with myocardial cell apoptosis and decreased cardiac function. However, at the early stage of pressure overload induced myocardial hypertrophy, increased myocardial autophagy was associated with a decrease in cardiac apoptosis and cardiac function. The changes of cardiac myocyte autophagy have not been fully elucidated. In this study, we investigated the relationship between myocardial autophagy and myocardial hypertrophy in a rat model of pressure overload induced by abdominal aortic coarctation. Model: male Sprague-Dawley rats weighing 180-200g underwent abdominal aorta constriction or abdominal aorta constriction, and set up sham-operated sham group. After successful modeling, the rats were killed at 1 h, 3 h, 6 h, 24 h, 48 h and 72 h, respectively. The rats were divided into three groups: 30 rats in the control group, and 5 rats in the sham operation group were killed at different time points at different time points (1 h, 3 h, 6 h, 24 h, 48 h, 72 h)) sham operation group (10 rats) were divided into two groups: the sham operation group (n = 10), the sham operation group (n = 10), the sham operation group (n = 10). Myocardial hypertrophy and myocardial autophagy: heart weight / body weight ratio: HW / BWR, left ventricular weight / body weight ratio LVW / BW, left ventricular mass / body weight ratio LVW / BW, left ventricular mass index (LVW / BW, left ventricular mass index). The changes of cardiac myocyte size were observed by HE staining. Western blot technique was used to detect the expression of autophagy related protein in myocardial tissue. Results compared with sham operation, the expression of autophagy related protein was detected at 1 h and 3 h after AAC. There was no significant change in cardiac weight and left ventricular mass index. There was a slight increase in HW / BW ratio at 6 h after AAC. There was a further increase in LVW / BW ratio at 24 h after AAC. There was a significant increase in LVW / BW ratio at 48 h and 72 h in AAC group as compared with sham operation sham group. He staining showed that the diameter of cardiomyocytes in AAC group was larger than that in Sham group at 72 h. The results of immunoblotting showed that the expression of LC3II/I ratio, Beclin1 and Atg12 protein in cardiomyocyte autophagy was significantly lower than that in sham-operated group. Conclusion: cardiac myocyte autophagy in rats at the early stage of pressure overload decreased progressively. The decrease of myocardial autophagy is related to myocardial hypertrophy, which suggests that the application of myocardial autophagy inducer may be beneficial to the prevention and treatment of myocardial hypertrophy at the early stage of pressure overload induced myocardial hypertrophy.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.2

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