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内洋地黄素拮抗剂对大鼠心肌缺血再灌注损伤的保护作用
引用本文:王德国,汪和贵,柯永胜,杨尚印. 内洋地黄素拮抗剂对大鼠心肌缺血再灌注损伤的保护作用[J]. 中国药理学通报, 2004, 20(8): 927-931
作者姓名:王德国  汪和贵  柯永胜  杨尚印
作者单位:皖南医学院弋矶山医院心脏科,安徽,芜湖,241001
基金项目:安徽省自然科学基金,安徽省教育厅自然科学基金
摘    要:目的 结扎大鼠左冠状动脉前降支造成心肌缺血再灌注损伤 (MIR) ,观察MIR时心肌组织内洋地黄素水平的变化和内洋地黄素特异性拮抗剂地高辛抗血清对MIR时心肌的保护作用。方法 采用左冠状动脉前降支结扎 30min ,复灌4 5min建立在体大鼠MIR模型。SpraugeDawley大鼠随机分成 7组 ,每组 10只。假手术组 ,缺血再灌注模型组 ,生理盐水组 ,维拉帕米组 ,小剂量、中剂量、大剂量地高辛抗血清组。各组于再灌注 4 5min后立即取左室心尖部缺血区心肌 ,检测心肌匀浆中内洋地黄素含量、心肌细胞膜Na+ ,K+ ATP酶活性和线粒体内Ca2 + 含量。光镜及电镜下观察心肌组织形态学变化。结果 MIR时心肌组织内洋地黄素水平明显升高 ,细胞膜Na+ ,K+ ATP酶活性明显下降 ,线粒体内Ca2 + 水平升高 ,心肌组织结构发生明显损伤。中、大剂量地高辛抗血清能降低心肌组织内洋地黄素水平 ,恢复心肌细胞膜Na+ ,K+ ATP酶活性 ,降低线粒体内Ca2 + 水平 ,减轻MIR导致的心肌组织结构的损伤。结论 内洋地黄素拮抗剂地高辛抗血清对MIR大鼠心肌有明显的保护作用 ,其作用机制可能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。

关 键 词:内洋地黄素  缺血再灌注损伤/心肌  腺苷三磷酸酶  地高辛抗血清  超微结构
文章编号:1001-1978(2004)08-0927-05
修稿时间:2003-09-03

Protective effects of endoxin antagonist on myocardial ischemia reperfusion injury in rats
WANG De guo,WANG He gui,KE Yong sheng,YANG Shang yin. Protective effects of endoxin antagonist on myocardial ischemia reperfusion injury in rats[J]. Chinese Pharmacological Bulletin, 2004, 20(8): 927-931
Authors:WANG De guo  WANG He gui  KE Yong sheng  YANG Shang yin
Abstract:Aim To research the changes of myocardial endoxin level in rats with myocardial ischemia reperfusion (MIR) and the protevtive effects of anti digoxin antiserum, an endoxin specific antagonist, on MIR injury. Methods Myocardial ischemia reperfusion injury models were obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprauge Dawley rats were randomly divided into seven groups each with 10 rats. There were sham group, MIR group, normal saline group, verapamil group, low dose anti digoxin antiserum group, middle dose anti digoxin antiserum group, and high dose anti digoxin antiserum group. After reperfusion of left ventricular myocardium, sample of ischemia were processed immediately. Myocardial endoxin levels, Na +, K + ATPase activities, and intramitochondrial Ca 2+ contents were measured. The myocardial morphology were observed. Results Myocardial endoxin levels were significantly increased; Na +, K + ATPase activities were remarkably decreased; intramitochondrial Ca 2+ contents were remarkably raised. Meanwhile, myocardial morphology injury were remarkable in light microscope and electric microscope. Middle and high dose of anti digoxin antiserum intervention, myocardial endoxin levels were remarkably decreased; Na +, K + ATPase activities were drastically increased; intramitochondrial Ca 2+ declined. The myocardial histological morphology was significantly improved. Conclusion Antidigoxin antiserum, an endoxin antagonist, had protective effect against MIR. The mechanism maybe related to antagonizing endoxin, restoring energy metabolism, attenuating intracellular Ca 2+ overload.
Keywords:endoxin  ischemia reperfusion injury/myocardium  adenosine triphosphatase  anti-digoxin antiserum  morphology/myocardium
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