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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(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2004年第6期
页码:
526-529
栏目:
基础研究
出版日期:
2004-11-01

文章信息/Info

Title:
Effects of endothel in-1 10-23 deoxyribozyme on acute ischemic arrhythmia in isolated perfused rat hearts
作者:
潘秀颉1; 林　丽1; 任安经1; 潘燕霞1; 王伟忠1; 袁文俊1; 潘燕霞2
1. 第二军医大学基础医学部生理学教研室,上海200433 ;2. 福建医科大学基础医学院生理与病理生理系,福建福州350004
Author(s):
PAN Xiu-jie1; LIN Li1; REN An-jing1; PAN Yan-xia1; WANG Wei-zhong1; YUAN Wen-jun1; PAN Yan-xia2
1. Department of Physiology , College of Basic Medical Sciences , Second Military Medical University ,Shanghai 200433 , China ;2. Department of Physiology and Pathophysiology , College of Basic Medical Sciences , Fujian Medical University , Fuzhou , Fujia
关键词:
10-23 脱氧核酶; 心律失常; 内皮素
Keywords:
10-23 deoxyribozyme ;  arrhythmia ;  endothelin
分类号:
R331. 31
DOI:
-
文献标识码:
A
摘要:
目的:应用内皮素(endothelin , ET)2- 10-23 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-1 10-23 脱氧核酶,作体外切割筛选;SD 大鼠静脉注射ET-1 10-23脱氧核酶,观察心肌对5’标记荧光素FAM 的ET-1 10-23 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-1 10-23 脱氧核酶在体外高效切割ET-1 RNA 底物;荧光标记ET-1 10-23 脱氧核酶静脉注射4 h 后,大鼠心肌组织内荧光广泛分布;静脉注射ET-1 10-23 脱氧核酶4 h 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-1 10223 脱氧核酶能有效切割ET-1 RNA ,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。
Abstract:
AIM: To examine the role of endogenous endothlin-1 ( ET-1) in the pathogenesis of acute ischemic arrhythmia in isolated perfused rat heart s 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 t ranscribed in vit ro and FAM-labeled 10-23 deoxyribozyme was used to select cleavable 10-23 deoxyribozymes in vit ro 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 heart s 4 h after the int ravenous injection of 10-23 deoxyribozyme in intact rat s. RESULTS : ET-1 10-23 deoxyribozyme efficiently cleft ET-1 RNA subst rates. 4 h after the int ravenous injection , wide dist ribution of FAM2labeled 10-23 deoxyribozyme was seen in the my-ocardium. The int ravenous administ ration of ET-1 10-23 deoxyribozyme significantly reduced arrhythmia score , total vent ricular premature beat s , vent rical tachycardia count s and duration of vent rical tachycardia and/ or vent rical fibrillation after occlusion of LAD in a dose2dependent manner , while 1023 deoxyribozyme with reverse arms had no significant effect s on acute arrhythmias. CONCLUSION: ET-1 10-23 deoxyribozyme designed in this study cleft ET-1 RNA subst rate efficiently and reduced the acute ischemic arrhythmias , which shows that endogenous ET-1 plays an important role in acute ischemic arrhythmia.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2003-12-12
更新日期/Last Update: 2004-11-01