Catalase-overexpressing transgenic mouse heart is resistant to ischemia-reperfusion injury
Catalase-overexpressing transgenic mouse heart is resistant to ischemia-reperfusion injury
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DOI：
10.1152/ajpheart.1997.273.3.h1090
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发表时间：
1997-09-01
影响因子：
4.8
通讯作者：
Kang, YJ
中科院分区：
文献类型：
--
作者：
Li, GQ;Chen, Y;Kang, YJ
心肌缺血再灌注损伤至少部分由氧自由基介导。过氧化氢酶是参与过氧化氢解毒的主要酶。心脏过氧化氢酶活性很低，这可能是心脏对缺血再灌注损伤高度敏感的原因之一。本研究旨在确定转基因小鼠心脏中过氧化氢酶特异性升高是否可以提供对缺血再灌注损伤的保护。心脏分离自转基因小鼠，其中心脏中的过氧化氢酶升高至类似于非转基因心脏的60倍以上，并从非转基因同窝出生的小鼠进行50分钟的温暖（37摄氏度）零流量缺血，然后再流90分钟。与非转基因对照组相比，转基因心脏显示出显著改善的收缩力恢复（在90分钟再灌注结束时为75%对25%，P < 0.01）。肌酸激酶的外排减少了类似50%，心肌梗死区划分的三苯基四唑在再灌注结束时减少了类似40%，在转基因心脏与非转基因对照组相比。这些发现支持了过氧化氢是缺血再灌注损伤的重要原因的观点，并提示过氧化氢酶活性升高可能提供保护。
Myocardial ischemia-reperfusion injury is at least partially mediated by oxygen-derived free radicals. Catalase is a major enzyme involved in the detoxification of hydrogen peroxide. The activity of catalase in the heart is very low, which may be a factor responsible for the high sensitivity of the heart to ischemia-reperfusion injury. The present study was undertaken to determine whether elevation of catalase specifically in the heart of transgenic mice can provide protection against ischemia-reperfusion injury. Hearts isolated from transgenic mice in which catalase in the heart was elevated similar to 60-fold higher than that in nontransgenic heart and from the nontransgenic littermates were subjected to 50 min of warm (37 degrees C) zero-flow ischemia followed by 90 min reflow. Compared with nontransgenic controls, transgenic hearts showed significantly improved recovery of contractile force (75 vs. 25% at the end of 90 min reperfusion, P < 0.01). Efflux of creatine kinase was reduced by similar to 50%, and the zone of myocardial infarction as demarcated by triphenyltetrazolium at the end of reperfusion was reduced by similar to 40% in transgenic hearts compared with nontransgenic controls. These findings support the view that hydrogen peroxide is an important cause of ischemia-reperfusion damage and suggest that protection may be provided by elevation of catalase activity.