β受体阻滞剂治疗后心率下降不同程度对心力衰竭大鼠的影响

发布时间：2018-01-08 15:23

  本文关键词：β受体阻滞剂治疗后心率下降不同程度对心力衰竭大鼠的影响　出处：《河北医科大学》2016年硕士论文　论文类型：学位论文

  更多相关文章： 心力衰竭 β受体阻滞剂 心率 β_1肾上腺素受体mRNA β_1肾上腺素受体蛋白表达

【摘要】：心力衰竭是各种类型心脏疾病的严重和终末阶段。在全球范围内,心力衰竭已经成为一个日益增长的健康问题,并且随着年龄的增加,发病率也不断上升。心力衰竭早期,心排血量降低,反射性地使交感神经系统兴奋性增加、心率加快。在一定范围内,心率加快可以使心输出量增加,然而心率增快超过一定范围时,心肌耗氧量增加、心室舒张期显著缩短、冠脉血流减少,从而加重心力衰竭。临床实验表明,静息心率每分钟增加5次,心血管死亡和心力衰竭住院的风险增加16%。β-受体(β-adrenergic receptor,β-AR)阻滞剂通过阻断β_1肾上腺素能受体(β_1-adrenergic receptor,β_1-AR),减慢心率,降低心肌耗氧量,改善心室充盈功能,改善心力衰竭患者的心功能和预后。本课题组前期的基础实验研究结果证实β_1-AR阻滞剂能够降低射血分数(EF)40%的心力衰竭大鼠的心率、上调β_1-AR mRNA表达水平、改善心功能参数。但是,心率降低和β_1-ARmRNA表达水平升高到一定程度,心功能并未得到进一步改善。此外,有研究显示在LVEF≥50%和LVEF50%的心肌梗死患者中,β-AR阻滞剂的治疗可以降低患者的死亡率。本课题研究心率下降不同程度时,心肌梗死后心力衰竭(40%≤EF60%)大鼠的心功能、左室质量指数(LVMI)、β_1-AR mRNA表达和蛋白表达水平的变化情况。探讨心率下降不同程度对心肌梗死后心力衰竭大鼠的心功能的影响。目的:研究β_1-AR阻滞剂使心率下降不同程度与心肌梗死后心力衰竭大鼠的心功能、LVMI、β_1-AR mRNA表达及蛋白表达变化的关系。方法:心肌梗死后心力衰竭大鼠模型制备采取的是手术结扎心脏冠状动脉左前降支的方法,假手术组大鼠单纯开胸,并不结扎冠状动脉。全部大鼠均于手术后4周实施超声心动图(UCG)检查,判定心力衰竭模型成功的标准是超声结果显示40%≤EF60%。手术后4周共有25只大鼠的超声结果符合心力衰竭的标准,根据β_1-AR阻滞剂治疗后心率下降的不同水平随机分为4组:G0组:心力衰竭对照组;G1组:心率下降35-45次/分;G2组:心率下降75-85次/分;G3组:心率下降115-125次/分。G0组和假手术组的大鼠均给予等容积的生理盐水灌胃,G1、G2和G3组大鼠均予以富马酸比索洛尔片灌胃,全部大鼠在达到目标心率后继续灌胃6周,6周后实施UCG检查。取材时测定大鼠左室心肌重量,计算LVMI。采用反转录-聚合酶链式反应(Reverse reaction PCR,RT-PCR)测定大鼠左心室非梗死区的心肌β_1-AR mRNA表达水平,使用蛋白质印迹法(Western Blot)检测大鼠左心室非梗死区心肌β_1-AR蛋白表达水平。结果:1超声心动图结果UCG检查分别在造模术后4周、富马酸比索洛尔片治疗6周后实施,以检测心功能指标。造模术后4周,G0、G1、G2和G3组大鼠的LVEDD、LVESD较假手术组增加,FS和EF较假手术组减低,差异均有统计学意义(P0.01)。与假手术组对比,G0、G1、G2和G3组大鼠的LVPWd、IVSd增加,差异有统计学意义(P0.05)。药物治疗前,G0、G1、G2和G3组大鼠UCG数据间均无统计学差异(P0.05)。富马酸比索洛尔片持续灌胃6周后,G1、G2组的FS、EF较G0组增高,差异有统计学意义(P0.05)。G3组的FS、EF与G0组相比,差异无统计学意义(P0.05)。与G0组相比,G1、G2组的LVEDD、LVESD有一定的改善,差异有统计学意义(P0.01)。G3组的LVEDD、LVESD与G0组相比,差异无统计学意义(P0.05)。G1、G2和G3组的IVSd、LVPWd与G0组相比,差异无统计学意义(P0.05)。2心率与血压变化给药前,采用MD3000型生物信号采集系统经鼠尾动脉测定全部大鼠的心率和血压。给药前,G1、G2、G3组与G0组大鼠的心率和血压水平相似,差异无统计学意义(P0.05)。比索洛尔灌胃6周后,G1组、G2组及G3组的大鼠心率分别下降了45.00±6.99次/分、78.83±7.60次/分、119.50±10.33次/分,差异有统计学意义(P0.01)。比索洛尔灌胃6周后,与G0组对比,G1组、G2组及G3组的血压水平的差异无统计学意义(P0.05)。3心室质量指数(LVMI)G1、G2、G3组大鼠的LVMI较G0组有所下降(P0.01),却仍高于假手术组(P0.05),差异有统计学意义。4非梗死区心肌组织β_1-AR mRNA和蛋白表达G0组大鼠的非梗死区心肌β_1-AR mRNA、蛋白表达水平低于假手术组,差异有统计学意义(P0.01)。药物治疗后,G1、G2组大鼠β_1-AR mRNA、蛋白表达水平较G0组升高(P0.01),但是仍低于假手术组(P0.01);G1与G2组的β_1-AR mRNA、蛋白表达水平无统计学差异(P0.05)。与G0组相比,G3组的β_1-AR mRNA升高,差异无统计学意义(P0.05),G3组的β_1-AR蛋白表达增加,差异有统计学意义(P0.01)。与G1和G2组比较,G3组β_1-AR mRNA、蛋白表达水平减低,差异有统计学意义(P0.05)。结论:心率降低35-45次/分组、75-85次/分组,不仅心功能有所改善,而且β_1-AR mRNA、蛋白表达也有所上调;然而心率持续降低,即心率降低115-125次/分组,心功能未见进一步改善,且β_1-AR mRNA、蛋白表达虽有所上调,仍低于心率降低35-45次/分组、75-85次/分组。
[Abstract]:Heart failure is of various types of heart disease and severe end stage. In the global scope, heart failure has become a growing health problem, and with the increase of age, the incidence is rising. The early stage of heart failure, cardiac output decreased, reflecting the increased excitability of the sympathetic nervous system, heart rate. Within a certain range, can make the heart rate, cardiac output increased, but the heart rate increased by more than a certain range, increased myocardial oxygen consumption, ventricular diastolic coronary blood flow decreased significantly shortened, thus increase the heart failure. The clinical experiments showed that resting heart rate increased 5 times per minute, the risk of cardiovascular death and heart failure hospitalization increased 16%. beta (-adrenergic beta receptor, -AR beta blockers) by blocking beta adrenergic receptor _1 (beta _1-adrenergic beta receptor, _1-AR), slow heart rate, reduce myocardial oxygen consumption, The improvement of ventricular filling function, improve cardiac function and prognosis of heart failure patients. Results the experimental study confirmed previous beta blockers can reduce _1-AR ejection fraction (EF) in rats with heart failure 40% heart rate, increase the expression level of mRNA beta _1-AR, improve heart function parameters. However, the heart rate decreased and the expression of _1-ARmRNA beta the level is increased to a certain extent, the heart function has not been improved. In addition, studies have shown that in patients with myocardial infarction LVEF = 50% and LVEF50% in the treatment of -AR beta blockers can reduce the mortality of patients. This study decreased heart rate, heart failure after myocardial infarction (40% EF60%) on heart function in rats, left ventricular mass index (LVMI), mRNA expression of _1-AR and protein expression levels. The study of heart rate decreased in different degree of heart failure after myocardial infarction in rats with heart function. Ring. Objective: To study the _1-AR beta blockers to heart rate, decreased with heart failure after myocardial infarction in rats LVMI, mRNA expression and protein expression of _1-AR. Methods: the relationship between the change of heart failure after myocardial infarction rat model is taken by the descending branch of the coronary artery ligating left anterior, false the rats of operation group received open chest, no ligation of coronary artery. All the rats were 4 weeks after surgery the implementation of echocardiography (UCG) examination, to determine the heart failure model of success is ultrasound ultrasound showed 40% EF60%. 4 weeks after surgery there were 25 rats with heart failure results according to different standards. The level of _1-AR were randomly divided into beta blockers in the treatment of heart rate falling into 4 groups: group G0: control group G1 group: heart failure; heart rate decreased 35-45 beats per minute; group G2: heart rate decreased 75-85 beats per minute; group G3:.G0 group decreased heart rate 115-125 times / min And the rats in sham operation group were given normal saline by gavage, G1, G2 and G3 group rats were given intragastric administration of Bisoprolol Fumarate Tablets, all the rats to gavage for 6 weeks to reach the target heart rate after 6 weeks after the implementation of UCG. Determination of left ventricular myocardium of rats were weight, calculated LVMI. using reverse transcription polymerase chain reaction (Reverse reaction PCR, RT-PCR) were non infarcted left ventricular myocardium _1-AR beta mRNA expression using Western blotting (Western Blot) detection of left ventricle in rats the expression of myocardial infarction _1-AR protein. Results: 1 the results of echocardiography examination respectively in UCG model 4 weeks after operation, Bisoprolol Fumarate Tablets after 6 weeks of treatment, in order to detect the indexes of heart function modeling. After 4 weeks, G0, G1, G2 and G3 group rats LVEDD, LVESD increased compared with sham group, FS and EF compared with the sham operation group decreased, the differences were statistically. 涔，

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