美托洛尔对慢性心力衰竭大鼠血流动力学及心脏重构影响的研究  

Effect of metoprolol on hemodynamic changes and cardiac remodeling in rats with chronic heart failure

作　　者：邝素华[1] 梁庆[2] 马伦超[1] 陆国梁[1] 杨超[1] 张英元[1] 廖胜杰 谢少波[1] 

机构地区：[1]广州医科大学附属第一医院心脏外科,广州510120 [2]广州医科大学附属第一医院急诊科,广州510120

出　　处：《岭南心血管病杂志》2016年第3期320-324,共5页South China Journal of Cardiovascular Diseases

基　　金：广东省医学科研基金(项目编号:A2013251);广州市医药卫生科技项目(项目编号:20131A011142);广州市医药卫生科技项目(项目编号:20151A011069);广州医科大学附属第一医院科研基金立项(项目编号:201216-gyfyy)

摘　　要：目的在体研究不同剂量美托洛尔(metoprolol,Meto)对慢性心力衰竭(heart failure,HF)大鼠血流动力学及心脏结构影响。方法100只SD大鼠按随机数字表法随机分为5组(每20只):(1)假手术组(sham组);(2)HF模型组(HF组);(3)Meto治疗小剂量组[MetoA组,1.25 mg/(kg.d)];(4)Meto治疗中剂量组[Meto B组,5 mg/(kg.d)];(5)Meto治疗大剂量组[Meto C组,20 mg/(kg.d)]。缩窄腹主动脉建立HF动物模型,术后第4周开始给药至第8周,术后第4周及第8周超声心动图及第8周取材前有创血流动力学方法测定血流动力学指标;心脏、肺脏取材后称质量及观察大鼠大体心脏结构改变。结果(1)MetoB组HF大鼠心脏收缩及舒张功能显著改善,而Meto C组HF大鼠心率显著减缓,左心室射血分数与HF组比较,差异无统计学意义(P>0.05);(2)Meto治疗组大鼠心脏随着Meto治疗剂量的增加而逐渐缩小,心肌肥厚逐渐改善;(3)不同剂量组间两两比较,心质量指数(心脏质量/体质量)随Meto治疗剂量的增加逐渐降低,差异有统计学意义(P<0.01);MetoB组肺质量指数(肺质量/体质量)亦较Meto A组降低,差异有统计学意义(P=0.003<0.01),而Meto C组肺质量指数则较Meto B组有所上升,差异有统计学意义(P=0.000<0.01)。结论在治疗剂量范围内,Meto治疗对HF大鼠血流动力学的改善有"天花板效应",对于心肌重构改变的逆转有"剂量依赖效应",中剂量Meto在HF大鼠中可获得最大的解剖病理和血流动力学获益。Objectives To study the in vivo effect of metoprolol （Meto） with various doses on hemodynamic changes and cardiac remodeling in rats with chronic heart failure （HF）. Methods Totally 100 Sprague-Dawley rats were randomly divided into 5 groups, 20 rats in each group： （1） sham group; （2） HF group; （3） low-dose Meto-treated group [Meto A group, 1.25 mg/（kg.d）]; （4） medium-dose Meto-treated group [Meto B group, 5 mg/（kg.d）]; （5） large-close Meto-treated group [Meto C group, 20 mg/（kg.d）]. Rats in HF group and Meto-treated groups were subjected to abdominal aortic ligation. Four weeks after operation, different doses of Meto were given for 4 weeks. Echocardiography was conducted to monitor the hemodynamic parameters at the forth and the eighth week after operation. Invasive hemodynamic examination was performed before rats were sacrificed at the eighth week. Harvested hearts and lungs of the rats were weighted and gross morphological changes were observed. Results （1） Systolic and diastolic function of HF rats in Meto B group significantly improved, while heart rate of HF rats in Meto C group significantly slowed, and ejection fraction in Meto C group had no significant difference with that in HF group （P〉 0.05）; （2）Heart size in Meto-treated groups decreased gradually as dose of Meto increased,with myocardial hypertrophy improving gradually; （3） Heart weight index （heart weight/body weight） decreased gradually with the increase of the therapeutic dose among Meto-treated groups （P〈O.O1） ; Lung weight index （lung weight/body weight） of Meto B group was lower than that of Meto A group （P=0.003 〈0.01 ）, while lung weight index of Meto C group was higher than that of Meto B group （P=0.000 〈0.01 ）. Conclusions In the therapeutic dose range, there was ＂a ceiling effect＂ of Meto treatment on the improvement in hemodynamic changes in HF rats, and ＂a dose-dependent effect＂ on the myocardial reverse remodeling. Medium-dose Meto therapy

关 键 词：心力衰竭 β-肾上腺素受体阻滞剂 美托洛尔 血流动力学 心肌重构 

分 类 号：R541.6[医药卫生—心血管疾病]