阿托伐他汀与螺内酯联合应用对大鼠心肌肥厚性重构的干预研究

发布时间：2018-09-12 18:33

【摘要】：背景心肌肥厚是心脏对急慢性血流动力学超负荷或非血流动力学因素的一种适应性反应,是原发性高血压、动脉粥样硬化、瓣膜病等疾病常见的并发症。可显著增加心力衰竭和心脏性猝死的风险。阿托伐他汀和螺内酯两种药物对于左室重构以及功能的改善均有较好的作用。目的本研究经缩窄腹主动脉制备心肌肥厚模型,评价联合应用阿托伐他汀与螺内酯对心肌肥厚性重构的有效性,以期为心肌肥厚的临床治疗提供实验依据。方法选用雄性SD大鼠,腹主动脉缩窄法制备心肌肥厚模型。造模六周后行超声监测,检测心内结构和功能。随后进行随机分组,前四组为模型组:A组:阿托伐他汀(10mg/kg),B组:螺内酯(20 mg/kg),C组:阿托伐他汀(10 mg/kg)+螺内酯(20 mg/kg);D组:生理盐水。E组为正常对照组。灌胃给药四周后,超声心动图测定左室后壁(LVPW)、左室内径(LVD)、室间隔(IVS)、收缩末期内径(LVS)、射血分数(LVEF)、短轴缩短率(LVFS),左室收缩压(LVSP)、舒张末压(LVEDP)、左室压力变化最大上升速率(dP/dtmax)、左室压力变化最大下降速率(dP/dtmin)及心肌能量消耗变化,对比各组之间的差异。结果1.和正常对照组相比,模型组LVPW、IVS、LVS、LVEDP及心肌能量消耗均明显增加,LVD、LVEF、LVFS、dp/dtmax、dp/tmin/LVSP则明显下降,差异具有统计学意义(P0.05)。提示大鼠心肌肥厚模型造模成功。2.A、B、C三组均可降低LVPW、IVS、LVS、LVEDP及心肌能量消耗,增加LVD、LVEF、LVFS、dp/dtmax、dp/tmin/LVSP,差异具有统计学意义(P0.05)。其中C组差异更为明显。D组大鼠用药前后各指标差异不明显,没有统计学意义(P0.05),即生理盐水对大鼠心脏功能各指标无影响。阿托伐他汀和螺内酯均可改善大鼠心脏功能,联合应用对心肌肥厚型大鼠效果更佳。结论1.单纯使用阿托伐他汀或螺内酯可增加大鼠的心功能,改善心室重构,促进大鼠得以良好的成长发育。2.阿托伐他汀和螺内酯联合应用对大鼠心肌左室重构、心脏功能和心肌能量消耗有着良好的协同作用,效果更为理想。
[Abstract]:Background Myocardial hypertrophy is an adaptive response of the heart to acute and chronic hemodynamic overload or non-hemodynamic factors. It is a common complication of essential hypertension, atherosclerosis, valvular disease and so on. It can significantly increase the risk of heart failure and sudden cardiac death. Both Atto vastatin and spironolactone have good effects on left ventricular remodeling and function improvement. Objective to study the effect of combined use of Atto vastatin and spironolactone on myocardial hypertrophy remodeling in order to provide experimental evidence for clinical treatment of myocardial hypertrophy. Methods Myocardial hypertrophy model was established by coarctation of abdominal aorta in male SD rats. Six weeks after modeling, ultrasonic monitoring was performed to detect the structure and function of the heart. The first four groups were divided into two groups randomly. The first four groups were model group: 10mg/kg group B group: spironolactone group (20 mg/kg) group C: Atto statin group (10 mg/kg) spironolactone group (20 mg/kg) group D: normal saline. Group E as normal control group. After four weeks of gavage, Echocardiographic measurement of left ventricular posterior wall (LVPW), left ventricular diameter (LVD), septal (IVS), end systolic diameter (LVS), fraction (LVEF), short axis shortening rate (LVFS), left ventricular systolic pressure (LVSP), end diastolic pressure (LVEDP), left ventricular pressure change maximum rise rate (dP/dtmax) left ventricular pressure change most Changes of dP/dtmin and myocardial energy consumption, The differences between the groups were compared. Result 1. Compared with the normal control group, the LVPW,IVS,LVS,LVEDP and myocardial energy consumption in the model group were significantly higher than those in the control group (P0.05). The results suggest that the success of rat model of myocardial hypertrophy. 2. The three groups can reduce LVPW,IVS,LVS,LVEDP and myocardial energy consumption, and increase LVD,LVEF,LVFS,dp/dtmax,dp/tmin/LVSP, has statistical significance (P0.05). Group C was more obvious. Group D rats before and after the treatment of each index difference was not significant (P0.05), that is, physiological saline did not affect the cardiac function of rats. Both Atto vastatin and spironolactone could improve cardiac function in rats. Conclusion 1. The use of Atto vastatin or spironolactone alone can increase cardiac function, improve ventricular remodeling, and promote the growth and development of rats. The combination of Atto vastatin and spironolactone has a good synergistic effect on left ventricular remodeling, cardiac function and myocardial energy expenditure in rats.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R965

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