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比索洛尔改善心力衰竭大鼠心功能的机制探讨 预览 被引量:1

Exploration of Bisoprolol Improving Cardiac Function in Heart Failure Rats
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摘要 目的:观察比索洛尔对心力衰竭大鼠心功能的影响,并探讨其机制.方法:80只SD大鼠随机选取10只为正常对照组,10只作为假手术组,假手术组腹腔注射10 ml/kg的生理盐水.造模过程中有15只死亡,左心室短轴缩短率不达标5只,40只成功造模大鼠按随机数字表法分成4组:模型组(n=10)、比索洛尔组(n=10)、卡托普利组(n=10)和比索洛尔+卡托普利组(n=10).观察各组大鼠心功能指标,酶联免疫吸附测定(ELISA)法检测血浆B型利钠肽水平,实时定量逆转录-聚合酶链式反应(RT-PCR)检测心肌miR-25-3p表达水平,免疫蛋白印迹试验(Western blot)检测心肌肌浆网钙ATP酶2a(SERCA2a)和受磷蛋白(PLB)表达水平,定磷法测定心肌SERCA2a活性.结果:与正常对照组比较,模型组大鼠心输出量、左心室短轴缩短率、左心室射血分数、心肌SERCA2a和PLB表达水平、SERCA2a/PLB比值和SERCA2a活性显著降低,血浆B型利钠肽水平和心肌miR-25-3p表达水平显著升高(P均〈0.01).与模型组比较,比索洛尔组、卡托普利组和比索洛尔+卡托普利组大鼠心输出量、左心室短轴缩短率、左心室射血分数、心肌SERCA2a和PLB表达水平、SERCA2a/PLB比值和SERCA2a活性显著升高,血浆B型利钠肽水平和心肌miR-25-3p表达水平显著降低(P均〈0.05).结论:比索洛尔可以改善心力衰竭大鼠心功能,机制可能与下调心肌miR-25-3p表达,提高SERCA2a和PLB表达,提升SERCA2a/PLB比值,增强SERCA2a活性有关. Objective: To observe the effect of bisoprolol on cardiac function in heart failure (HF) rats and to explore the mechanism. Methods: The experimental rats were divided into 6 groups: Control group, with normal healthy rats, Sham group, the rats received intraperitoneal injection of normal saline; chronic heart failure (CHF) model was successfully established in 40 rats and divided into 4 groups: CHF group, CHF+bisoprolol (Bis) group, CHF+captopril (Cap) group and CHF+Bis and Cap group.n=10 in each group. The cardiac function was observed among different groups; plasma BNP level was measured by ELISA, myocardial miR-25-3p expression was examined by RT-PCR, protein expressions of SERCA2a and phospholamban (PLB) were detected by Western blot analysis and SERCA2a activity was determined by inorganic phosphorus method. Results: Compared with Control group, CHF group showed decreased cardiac output (CO), left ventricular fractional shortening (LVFS), left ventricular ejection fraction (LVEF), reduced expression of cardiac SERCA2a, PLB, the ratio of SERCA2a/PLB and SERCA2a activity; while increased plasma BNP and miR-25-3p expression, allP〈0.01. Compared with CHF group, CHF+Bis, CHF+Cap and CHF+Bis and Cap groups had increased CO, LVFS, LVEF, elevated expression of cardiac SERCA2a, PLB, the ratio of SERCA2a/PLB and SERCA2a activity; while decreased plasma BNP and miR-25-3p expression, allP〈0.05.Conclusion: Bisoprolol could improve cardiac function in HF rats, which might be related to down regulating myocardial miR-25-3p expression, up regulating myocardial protein expressions of SERCA2a, PLB and enhancing SERCA2a activity.
作者 吴锦波 叶小汉 冼绍祥 董明国 WU Jin-bo, YE Xiao-han, XIAN Shao-xiang, DONG Ming-guo. (Department of Cardiology, Central Hospital of Dongguan City, Dongguan (510405), Guangdong, China)
出处 《中国循环杂志》 CSCD 北大核心 2017年第3期274-278,共5页 Chinese Circulation Journal
关键词 心力衰竭 肌细胞 心脏 微小核糖核酸 Heart failure Myocyte cardiac MicroRNA
作者简介 通讯作者吴锦波副主任医师博士研究方向为心力衰竭的诊治Email:wujinbocn@163.com
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