大鼠右冠状动脉右缘支结扎制备心动过缓模型  

Bradycardia model induced by right marginal branch of right coronary artery ligation in rats

作　　者：汤依群 冯凯 梁时雨 吴启权 潘奕彤 刘婷婷 TANG Yi-qun;FENG Kai;LIANG Shi-yu;WU Qi-quan;PAN Yi-tong;LIU Ting-ting(School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学基础医学与临床药学学院,江苏南京211198

出　　处：《中国药理学与毒理学杂志》2018年第5期385-391,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技重大专项(2011ZX09401-021)~~

摘　　要：目的制备与临床发病机制相关且重现性好的缺血性心动过缓模型。方法雄性SD大鼠18只,随机分为左冠状动脉结扎组、右冠状动脉结扎组和假手术组,每组6只。麻醉开胸,心电图监护下结扎左、右冠状动脉分支,分别在术后第5天(d5),d10和d15记录Ⅱ导联心电图,观察心电图和心率的变化;d16测量大鼠血流动力学参数,评价大鼠心功能;大鼠处死后,剪取含窦房结的右心房组织,HE和Masson染色观察右心房组织形态改变;Western蛋白印迹法测定右心房钠钙交换蛋白1(NCX1)和超极化激活环核苷酸门控阳离子通道亚型4(HCN4)蛋白的表达。结果与假手术组相比,结扎左、右冠状动脉大鼠心电图ST段均抬高(P<0.01),右冠状动脉结扎上升幅度较左冠状动脉结扎小(P<0.01);右冠状动脉结扎大鼠术后心率持续降低,d10后心率低于假手术对照组(P<0.05);左冠状动脉结扎大鼠术后心率呈升高回落趋势,d5心率高于假手术对照组(P<0.05),然后回落,d15回落到假手术组水平;左冠状动脉结扎后15 d,大鼠左心室内压最大下降速率明显下降(P<0.01),左心室终末舒张压显著上升(P<0.01);右冠状动脉结扎术对血流动力学指标均无明显影响。组织形态检查结果显示,右冠状动脉结扎引起右心房炎性浸润和纤维化更为明显(P<0.01);Western蛋白印迹结果显示,右心房组织(包含窦房结)NCX1和HCN4表达显著降低(P<0.05)。结论大鼠右冠状动脉结扎,引起右心房缺血性改变,成功制备了缺血性心动过缓模型。OBJECTIVE To establish a novel rat bradycardia model induced by ischemia injury.METHODS Eighteen male SD rats were divided into 3 groups（6 rats per group）： right marginal branch of right coronary artery（RMA） ligation group, left anterior descending artery（LAD） ligation group and sham-operated group. Rats had their chests opened after being anesthetized with 10% chloral hydrate（ip, 300 mg·kg-1）. Then, the LAD and RMA were ligated when monitored by BL-420 S biological data acquisition and analysis system. The ECG was recorded respectively on the 5 thday（d5）, d10 and d15 after surgery. The cardiac function of rats was evaluated by measuring hemodynamic parameter on d16. After rats were sacrificed, the right atrium tissue containing the sinoatrial node was cut to detect histopathological changes and the expressions of sodium calcium exchanger 1（NCX1） and hyperpolarization activated cyclic nucleotide gated cation channel 4（HCN4） by HE staining, Masson staining and Western blotting. RESULTS Compared with the sham-operated group, both LAD and RMA ligation could induce the ST segment elevation, but RMA ligation was not elevated as much as LAD ligation（P〈0.01）. The heart rate of rats decreased consistently after RMA ligation and was lower than that of shamoperated rats on d10 after operation（P〈0.05）. The heart rate showed a wave of rise and fall after LAD ligation. The heart rate became higher on d5 than that of control group and was reduced to the level of control group later on d15（P〈0.05）. About 15 d after operation, the maximal rate of decline of ventricular pressure（-dp/dtmax） was significantly decreased（P〈0.01） and the left ventricular end-diastolic pressure（LVEDP） was elevated obviously（P〈0.01） in LAD ligation rats while the cardiac function parameters were not changed in RMA ligation rats. HE staining and Masson staining results showed respectively that the inflammatory infiltration and fibrosis of the right atrium were more obvious in RMA ligati

关 键 词：冠状动脉 心动过缓 钠钙交换蛋白1 环核苷酸门控阳离子通道亚型4蛋白 

分 类 号：R965[医药卫生—药理学]