美托洛尔预处理对大鼠冠状动脉微栓塞后心肌细胞凋亡及天冬氨酸特异性半胱氨酸蛋白酶-8活化的影响及意义  

Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation aftercoronary microembolization in rats

作　　者：苏强[1] 李浪[1] 周游[1] 王江友[1] 文伟明[1] 陆永光[1] 

机构地区：[1]广西医科大学第一附属医院心内科广西心血管病研究所,南宁530021

出　　处：《中华心血管病杂志》2013年第8期693-697,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金（30760262/C030313）

摘　　要：目的探讨美托洛尔对大鼠冠状动脉微栓塞（CME）后心肌细胞凋亡及天冬氨酸特异性半胱氨酸蛋白酶（caspase）-8活化的影响及意义。方法45只大鼠按随机数字法分为微栓塞组（CME组）、假手术组、CME＋美托洛尔组，每组15只。经左心室注入微栓塞球构建CME模型；假手术组注射生理盐水代替微栓塞球；CME＋美托洛尔组术前30min内从大鼠尾静脉注射美托洛尔2．5mg／kg，共3次，每次间隔10min。各组术后6h分别应用心脏超声检测心功能，用切口末端标记法检测心肌细胞凋亡，免疫印迹法检测活化caspase．3及caspase-8的表达。结果与假手术组比较，CME组左心室射血分数（LVEF）[（72．68±3．26）％比（82．64±3．43）％，P〈0．05]、左心室短轴缩短率[（37．46±2．38）％比（42．85±3．25）％]和心排血量[（0．101±0．006）L／min比（0．162±O．008）L／min]较低，左心室舒张期末径[（6．22±0．17）mm比（5．18±0．43）mm]较高（均P〈0．05）；与CME组比较，CME＋美托洛尔组心功能[LVEF：（73．94±4．22）％；左心室短轴缩短率：（38．53±2．03）％；心排血量：（0．120±0．012）L／min；左心室舒张期末径：（6．18±0．27）mm]未见明显改善（P〉0．05）。与假手术组比较，CME组心肌细胞凋亡率（3．19％±1．23％比0．18％±0．10％）、活化的caspase-5、caspase-8含量较高（均P〈0．05）；与CME组比较，CME＋美托洛尔组心肌细胞凋亡率（1．32％±0．28％）、活化的caspase-3、caspase．8含量较少（均P〈0．05）。结论美托洛尔预处理治疗明显减少CME后心肌凋亡，其机制可能是阻断心肌细胞凋亡caspase-8介导的死亡受体凋亡途径的激活。Objective To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization （ CME ） in rats. Methods Adult rats were randomly assigned into CME group （intraventricular injection of 3000 microspheres with 42 μm in diameter） , sham- operated group （0. 1 ml saline ） and CME plus metoprolol group （pretreatment with 3 bolus metoprolol 2.5 mg/kg intravenous injection at 10 minutes interval at 30 minutes before microspheres injection, n = 15, each group ）. Cardiac function was evaluated by echocardiography at 6 hours post various treatments. Cardiomyocyte apoptosis was detected with TUNEL staining and the expression of caspase-3 and caspase-8 was detected with Western blot analysis. Results Compared with sham-operated group, LVEF （72. 68% ±3.26% vs. 82. 64% ± 3.43% ,P 〈 0. 05 ）, fractional shortening （FS） （37.46% ±2. 38% vs. 42. 85% ±3.25%） and cardiac output （CO） [（0.101 ±0.006） L/rain vs. （0.162±0.008） L/rain were significantly reduced while left ventricular end-diastolic diameter （ LVEDd ） [ （ 6.22± 0. 17 ）mm vs. （5. 18±0. 43） mmJ was significantly increased in CME group （all P 〈0. 05）. Cardiac function [ LVEF：73.94%±4. 22% ,FS：38.53% ±2. 03% ,CO： （0. 120 ±0. 012） L/min,LVEDd： （6. 18 ±0. 27） mm] was similar in CME plus metoprolol group compared to CME group （ all P 〉 0.05 ）. The cardiomyoeytes apoptosis rates （3.19% ±1.23% vs. 0.18%±0.10% ） and the levels of activated caspase-3 and caspase-8 proteins were significantly increased in CME group than in sham-operated group （ all P 〈 0. 05 ）. The cardiomyocyte apoptosis rate （1.32%± 0. 28% ） and the levels of activated caspase-3 and caspase-8 proteins were significantly lower in CME plus metoprolol group than in CME group （all P 〈0.05）. Conclusions Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway.

关 键 词：冠状血管 栓塞 美托洛尔 细胞凋亡 

分 类 号：R543.3[医药卫生—心血管疾病]