美托洛尔对心力衰竭大鼠血流动力学及Bcl-2、Bax蛋白表达的影响  

Effects of metoprolol on hemodynamics and expression of Bcl-2 and Bax proteins in heart failure rats

作　　者：梁庆[1] 黄敏坚[1] 邝素华[2] 黄伟青[1] 郭敏军[1] 郭锻强[1] 晏平[1] 刘荣[1] 林俊敏[1] 梁子敬[1] 

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

出　　处：《广东医学》2015年第12期1829-1833,共5页Guangdong Medical Journal

基　　金：广东省医学科研基金立项课题(编号:A2013251);广州市医药卫生科技项目(编号:20131A011142);广州市医药卫生科技一般引导项目(编号:20151A011069);广州医学院第一附属医院2012年度科研基金立项课题(编号:201216-gyfyy)

摘　　要：目的探讨不同剂量美托洛尔(Meto)对心力衰竭大鼠血流动力学及凋亡相关蛋白Bcl-2、Bax表达的影响。方法 SD大鼠100只随机分为5组(n=20):sham组不结扎腹主动脉,其余操作同HF组;HF组次全结扎腹主动脉;Meto小剂量组、Meto中剂量组、Meto大剂量组大鼠次全结扎腹主动脉术后第4周开始给Meto,剂量依次为1.25、5、20 mg/(kg·d),至第8周。术后第8周测定有创血流动力学指标后取材称量全心湿重(HW)、全肺湿重(LW),计算心重指数(全心重量/体重,HW/BW)、肺重指数(肺重/体重比,LW/BW),Western blot检测心肌抗凋亡基因Bcl-2与促凋亡基因Bax蛋白表达水平。结果 Meto各剂量组大鼠右心室收缩压(LVSP)及左心室压变化速率最大值(±dp/dt max)较HF组升高(P<0.01),Meto各剂量组左心室舒张压(LVDP)、左室舒张末期压(LVEDP)及-dp/dt max较HF组降低(P<0.01),Meto大剂量组LVSP较Meto小剂量组、Meto中剂量组明显降低(P<0.01),Meto大剂量组+dp/dt max较Meto中剂量组明显降低(P=0.002);而Meto大剂量组+dp/dt max与Meto小剂量组比较,Meto大剂量组LVDP、LVEDP及-dp/dt max与Meto中剂量组比较差异均无统计学意义(P>0.05)。HW/BW随Meto治疗剂量的增加逐渐降低(P<0.01);Meto中剂量组LW/BW较Meto小剂量组降低(P=0.003),而Meto大剂量组LW/BW则较Meto中剂量组有所上升(P=0.000)。HF组大鼠心脏Bcl-2/Bax比值较sham组降低(P<0.05),而随着Meto治疗剂量的增加Meto各剂量组的Bcl-2/Bax比值较HF组逐渐增加。且小剂量组比值与sham组相当,中剂量组出现比值翻转。结论中剂量Meto治疗在HF大鼠中可在获得解剖病理和抗凋亡获益的同时,保证最大的血流动力学获益,而大剂量Meto治疗则可能限制心功能进一步改善。Objective To investigate the effects of metoprolol （Meto） by different doses on hemodynamics and the myocardial expression of apoptosis related icrotein Be1 - 2 and Bax in heart failure rats. Methods One hundred Sprague - Dawley rats were randomly divided into 5 groups （ n = 20 ） ： sham group （ subjected to the same operation with the HF group but without ligation of abdominal aorta） , HF group （ subjected to the subtotal ligation of abdominal aorta） , Meto A group[subjected to the subtotal ligation of aodominal aorta and given with Meto 1.25 mg/（ kg·d） 1, Meto B group [ subjected to the subtotal ligation of abdominal aorta and given with Meto 5 mg/（ kg·d） ], Meto C group [ subjected to the subtotal ligation of abdominal aorta and given with Meto 20 mg/（ kg·d） ]. Different doses of Meto were given to the Meto treated groups 4 weeks after operation for 8 weeks. Invasive hemodynamic examination was performed before sacrificing, and weighing heart wet weight （ HW）, lung wet weight （ LW）, heart weight index （ heart weight/body weight, HW/ BW） and the pulmonary weight index （lung weight/body weight, LW/BW） were calculated. Anti -apoptotic gene Bcl - 2 and pro - apoptotic gene Bax protein expression was assessed by western blotting. Results Compared with the HF group rats, the LVSP and ＋ dp/dt max of the Meto treatment groups were significantly increased （P 〈 0. 01 ）, with significantly reduced LVDP, LVEDP and -dp/dt max （P 〈0. 01）. Compared with Meto A and Meto B groups, LVSP of Meto C group was significantly reduced （ P 〈0. 01 ）, and ＋ dp/dt max of Meto C group was significantly lower than that of Meto B group （P 〈0. 01 ）. There was no significant difference in ＋ dp/dt max between Meto C group and Meto A group, neither in LVDP, LVEDP nor - dp/dt max between Meto C and Meto B group. The HW/BW gradually decreased with increasing Meto dose （P 〈 0. 01 ）. Compared with Meto A group, LW/BW of Meto B group was significantly reduced （P 〈

关 键 词：心力衰竭 美托洛尔 心肌细胞凋亡 肾上腺素受体 心肌重塑 

分 类 号：R654.1[医药卫生—外科学]