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内皮素-1 10-23脱氧核酶对离体灌流大鼠心脏急性缺血性心律失常的影响
引用本文:潘秀颉,林丽,任安经,潘燕霞,王伟忠,袁文俊. 内皮素-1 10-23脱氧核酶对离体灌流大鼠心脏急性缺血性心律失常的影响[J]. 心脏杂志, 2004, 16(6): 526-529. DOI: 10.13191/j.chj.2004.06.34.panxx.009
作者姓名:潘秀颉  林丽  任安经  潘燕霞  王伟忠  袁文俊
作者单位:1. 第二军医大学基础医学部生理学教研室,上海,200433
2. 第二军医大学基础医学部生理学教研室,上海,200433;福建医科大学基础医学院生理与病理生理系,福建,福州,350004
基金项目:973国家重点基础研究发展规划课题 (G2 0 0 0 0 5 6 90 5 ),国家自然科学基金 (30 0 70 30 6 )
摘    要:目的 :应用内皮素 (endothelin ,ET) 110 2 3脱氧核酶抑制内源性ET 1表达 ,探讨内源性ET 1在急性缺血性心律失常发生中的作用。方法 :设计并合成ET 110 2 3脱氧核酶 ,作体外切割筛选 ;SD大鼠静脉注射ET 110 2 3脱氧核酶 ,观察心肌对 5’标记荧光素FAM的ET 110 2 3脱氧核酶的摄取和对其后离体灌流大鼠心脏左冠状动脉前降支结扎致急性缺血性心律失常的影响。结果 :设计合成的ET 110 2 3脱氧核酶在体外高效切割ET 1RNA底物 ;荧光标记ET 110 2 3脱氧核酶静脉注射 4h后 ,大鼠心肌组织内荧光广泛分布 ;静脉注射ET 110 2 3脱氧核酶4h后 ,左冠状动脉前降支结扎引起的急性缺血性心律失常显著减轻 ,并呈剂量依赖性 ,而对照序列无此效应。结论 :本实验设计的ET 110 2 3脱氧核酶能有效切割ET 1RNA ,减轻急性缺血性心律失常的发生 ,证明内源性ET 1在急性缺血性心律失常的发生中起重要作用。

关 键 词:10-23脱氧核酶   心律失常   内皮素
文章编号:1009-7236(2004)06-0526-04
修稿时间:2003-12-12

Effects of endothelin-1 10-23 deoxyribozyme on acute ischemic arrhythmia in isolated perfused rat hearts
PAN Xiu-jie,LIN Li,REN An-jing,PAN Yan-xia_,,WANg Wei-zhong,YUAN Wen-jun_. Effects of endothelin-1 10-23 deoxyribozyme on acute ischemic arrhythmia in isolated perfused rat hearts[J]. Chinese Heart Journal, 2004, 16(6): 526-529. DOI: 10.13191/j.chj.2004.06.34.panxx.009
Authors:PAN Xiu-jie  LIN Li  REN An-jing  PAN Yan-xia_    WANg Wei-zhong  YUAN Wen-jun_
Affiliation:PAN Xiu-jie1,LIN Li1,REN An-jing1,PAN Yan-xia_1,2,WANg Wei-zhong1,YUAN Wen-jun_1**
Abstract:AIM: To examine the role of endogenous endothlin-1(ET-1) in the pathogenesis of acute ischemic arrhythmia in isolated perfused rat hearts by decreasing ET-1 expression with ET-1 mRNA cleaving 10-23 deoxyribozyme. METHODS: ET-1 10-23 deoxyribozymes were designed and synthesized. ET-1 RNA was transcribed in vitro and FAM-labeled 10-23 deoxyribozyme was used to select cleavable 10-23 deoxyribozymes in vitro and detect uptake in the myocardium. Acute ischemic arrhythmia produced by occlusion of the left anterior descending branch of coronary artery(LAD) was observed in isolated perfused rat hearts 4 h after the intravenous injection of 10-23 deoxyribozyme in intact rats. RESULTS: ET-1 10-23 deoxyribozyme efficiently cleft ET-1 RNA substrates. 4 h after the intravenous injection, wide distribution of FAM-labeled 10-23 deoxyribozyme was seen in the myocardium. The intravenous administration of ET-1 10-23 deoxyribozyme significantly reduced arrhythmia score, total ventricular premature beats, ventrical tachycardia counts and duration of ventrical tachycardia and/or ventrical fibrillation after occlusion of LAD in a dose-dependent manner, while 10-23 deoxyribozyme with reverse arms had no significant effects on acute arrhythmias. CONCLUSION: ET-1 10-23 deoxyribozyme designed in this study cleft ET-1 RNA substrate efficiently and reduced the acute ischemic arrhythmias, which shows that endogenous ET-1 plays an important role in acute ischemic arrhythmia.
Keywords:deoxyribozyme  arrhythmia  endothelin
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