부산대학교 도서관

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 protein Bcl-2 and Bax in heart failure rats.Methods One hundred Spra-gue-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 abdominal aorta and given with Meto 1.25 mg/(kg· d)], 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 sacrifi-cing, 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<0.01), but LW/BW of Meto C group was significantly increased while compared with Meto B group (P<0.01).The myocardial Bcl-2/Bax ratio in HF group was significantly reduced while compared with sham group ( P<0.05 ) , and with the in-crease in Meto treatment groups, Bcl-2/Bax ratio of Meto treatment groups were gradually increased, which was flipped over in Meto B group.Conclusion Medium-dose of Meto in HF rats can obtain anatomic pathological and anti-apopto-sis benefit and ensures maximum hemodynamic benefit at the same time, but large-dose Meto treatment may inhibit fur-ther improvement of the heart function.