Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice
Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice
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DOI：
10.1006/jmcc.1998.0789
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发表时间：
1998-11-01
影响因子：
5
通讯作者：
Chua, BHL
中科院分区：
文献类型：
--
作者：
Chen, ZY;Siu, B;Chua, BHL
再灌流时产生的自由基被认为是缺血/再灌流损伤的主要原因之一。本实验旨在研究锰超氧化物歧化酶(MnSOD)在转基因小鼠体内过表达对脑缺血再灌注损伤的影响。表达了一种1.4kb的人MnSOD基因，转基因小鼠心脏中的MnSOD活性增加了325%，而其他抗氧化酶和热休克蛋白没有变化。免疫细胞化学研究表明，转基因小鼠心脏线粒体中的MnSOD标记增加。当这些心脏在全脑缺血35min后作为Langendorff制剂灌流45min时，转基因心脏的功能恢复率为52+/-4%，而非转基因心脏的功能恢复率为31+/-4%。这种保护伴随着转基因心脏乳酸脱氢酶释放的显著减少。在左冠状动脉结扎模型中，MnSOD的过表达限制了体内的心肌梗死范围。我们的结果表明，MnSOD的过度表达使心脏对缺血/再灌注损伤具有更强的抵抗力。(C)1998年学术出版社。
Generation of free radicals upon reperfusion has been cited as one of the major causes of ischaemia/reperfusion injury. The following series of experiments was designed to study the effect of manganese superoxide dismutase (MnSOD) overexpression in transgenic mice on ischemia/reperfusion injury. A species of 1.4 kb human MnSOD mRNA was expressed, and a 325% increase in MnSOD activity was detected in the hearts of transgenic mice with no changes in the other antioxidant enzymes or heat shock proteins. Immunocytochemical study indicated an increased labeling of MnSOD mainly in the heart mitochondria of the transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x left ventricular developed pressure, was 52 +/- 4% in the transgenic hearts as compared to 31 +/- 4% in the non-transgenic hearts. This protection was accompanied by significant decrease in lactate dehydrogenase release from the transgenic hearts. Overexpression of MnSOD limited the infarct size in vivo in a left coronary artery ligation model. Our results demonstrate that overexpression of MnSOD renders the heart more resistant to ischemia/reperfusion injury. (C) 1998 Academic Press.