内洋地黄素介导大鼠心肌缺氧复氧损伤的实验研究  

The study of myocardial anoxia-reoxygenation injury induced by endoxin in rats

作　　者：汪和贵[1] 柯永胜[1] 王德国[1] 杨尚印[1] 

机构地区：[1]皖南医学院弋矶山医院心内科,芜湖241001

出　　处：《中华急诊医学杂志》2005年第4期289-293,共5页Chinese Journal of Emergency Medicine

基　　金：安徽省自然科学基金资助项目(01043902);安徽省教育厅自然科学基金资助项目(99jl0219;2001kj0256)

摘　　要：目的研究内洋地黄素在离体大鼠心脏缺氧复氧损伤中的变化,观察内洋地黄素特异性拮抗剂地高辛抗血清对大鼠心脏缺氧复氧损伤的保护作用,明确内洋地黄素在心脏缺氧复氧损伤中的作用与机制。方法制备离体大鼠心脏缺氧复氧损伤模型,SD大鼠随机分为6组(n=10):正常对照组,缺氧复氧损伤组,维拉帕米组,小剂量、中剂量、大剂量地高辛抗血清组。连续记录各组心外膜ECG、HR、LVDP、±dp/dtmax。各组于复氧灌流结束时,取左心室心肌组织测定心肌匀浆中内洋地黄素含量、MDA含量、细胞膜Na+K+ATP酶活性以及线粒体内Ca2+水平。结果缺氧复氧损伤组ECG表现为ST段显著抬高,心率减慢,LVDP和±dp/dtmax显著降低,于复氧灌流早期出现严重室性心律失常;心肌组织内洋地黄素水平和MDA含量明显升高,细胞膜Na+K+ATP酶活性明显下降,线粒体内Ca2+水平显著升高。中、大剂量地高辛抗血清能明显降低心肌组织内洋地黄素水平和MDA含量,恢复心肌细胞膜Na+K+ATP酶活性,降低线粒体内Ca2+水平,改善心肌缺血性ST段抬高,显著改善血流动力学,拮抗再灌注引起的室性心律失常。结论地高辛抗血清通过拮抗内洋地黄素,恢复心肌细胞膜Na+K+ATP酶活性,减轻细胞内Ca2+超载,对缺氧复氧损伤心肌有明显的保护作用。表明内洋地黄素是介导心肌缺氧复氧损伤的重要?Objective To investigate the changes of endoxin during myocardial anoxia-reoxygenation injury,and to study whether endoxin special antagonist anti-digoxin antiserum has a protective effect against myocardial anoxia-reoxygenation injury, and to determine its mechanism on myocardial anoxia-reoxygenation injury. Methods The isolated Langendorff perfused rat heart model was established. Sixty Sprague Dawley(SD)rats were randomly divided into six groups and each group had 10 rats: normal control group, anoxia-reoxygenation group, verapamil group, low dose-, middle dose-, high dose anti-digoxin antiserum group. The electrocardiography (ECG), heart rate (HR), left ventricular development pressure (LVDP)and it's first derivative(±dp/dt max)were continuously recorded. The activity of Na +-K +-ATPase, endoxin, malondiadehyde(MDA)and mitochondrial Ca 2+ contents in myocardial tissues were measured.Results The anoxia-reoxygenation group showed a significant elevation on ST segments of epicardial ECG, an obvious decrease in HR, LVDP and ±dp/dtmax, more severe ventricular arrhythmias at early stage of reoxygenation; a remarkable increase in endoxin level and MDA content in myocardial tissues and mitochondrial Ca 2+ content, an obvious decrease in Na +-K +-ATPase activity in cell membrane. Middle, high anti-digoxin antiserum could relieve the elevation on ST segments at anoxia, antagonize the ventricular arrhythmias induced by reoxygenation, improve abnormal hemodynamics remarkably, decrease the levels of endoxin and MDA in myocardial tissues and the level of mitochondrial Ca 2+, recovery the activities of Na +-K +-ATPase in cell membrane. Conclusion Anti-digoxin antiserum has an obvious protective effect on myocardial anoxia-reoxygenation injury. Its mechanism may be related to antagonize endoxin, recover Na +-K +-ATPase activity in cell membrane and relieve intracellular Ca 2+ overload. The present experiment demonstrates that endoxin is one of major factors that induce myocardial anoxia-reoxygenation injury.

关 键 词：缺氧复氧损伤 内洋地黄素 NA^+-K^+-ATP酶活性 实验研究 大鼠心肌 介导 地高辛抗血清 严重室性心律失常 离体大鼠心脏 MDA含量 心肌细胞膜 特异性拮抗剂 心肌组织 线粒体内 保护作用 正常对照组 ST段抬高 血流动力学 损伤模型 SD大鼠 维拉帕米 心率减慢 LVDP EC 

分 类 号：R541[医药卫生—心血管疾病]