Overexpression of CuZnSOD in coronary vascular cells attenuates myocardial ischemia/reperfusion injury
Overexpression of CuZnSOD in coronary vascular cells attenuates myocardial ischemia/reperfusion injury
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DOI：
10.1016/s0891-5849(00)00363-4
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发表时间：
2000-10-01
影响因子：
7.4
通讯作者：
Chua, BHL
中科院分区：
文献类型：
--
作者：
Chen, ZY;Oberley, TD;Chua, BHL
超氧化物歧化酶清除氧自由基，氧自由基与心脏缺血/再灌注 (I/R) 损伤有关。我们的实验旨在研究铜/锌超氧化物歧化酶 (CuZnSOD) 适度增加对 TgN(SOD1)3Cje 转基因小鼠心肌 I/R 损伤的影响。表达了一种0.8 kb的人类CuZnSOD mRNA，在转基因小鼠的心脏中检测到CuZnSOD活性增加了273%，而其他抗氧化酶的活性没有变化。此外，免疫印迹分析显示 HSP-70 或 HSP-25 水平没有变化。免疫细胞化学研究表明，内皮细胞和平滑肌细胞的胞浆部分中的 CuZnSOD 标记增加，但转基因小鼠心脏的肌细胞中没有增加。当这些心脏在整体缺血 35 分钟后以 Langendorff 制剂灌注 45 分钟时，转基因心脏中心脏的功能恢复（以心率 x LVDP 表示）为 48 +/- 3%，而非转基因心脏中为 30 +/- 5% (p < .05)。心脏功能的改善伴随着转基因心脏中乳酸脱氢酶释放的显着减少。我们的结果表明，冠状血管细胞中 CuZnSOD 的过度表达使心脏对 I/R 损伤具有更强的抵抗力。 (C) 2000 爱思唯尔科学公司。
Superoxide dismutase scavenges oxygen radicals, which have been implicated in ischemia/reperfusion (I/R) injury in the heart. Our experiments were designed to study the effect of a moderate increase of copper/zinc superoxide dismutase (CuZnSOD) on myocardial I/R injury in TgN(SOD1)3Cje transgenic mice. A species of 0.8 kb human CuZnSOD mRNA was expressed, and a 273% increase in CuZnSOD activity was detected in the hearts of transgenic mice with no changes in the activities of other antioxidant enzymes. Furthermore, immunoblot analysis revealed no changes in the levels of HSP-70 or HSP-25 levels. Immunocytochemical study indicated that there was increased labeling of CuZnSOD in the cytosolic fractions of both endothelial cells and smooth muscle cells, but not in the myocytes of the hearts from 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 LVDP, was 48 +/- 3% in the transgenic hearts as compared to 30 +/- 5% in the nontransgenic hearts (p < .05). The improved cardiac function was accompanied by a significant reduction in lactate dehydrogenase release from the transgenic hearts. Our results demonstrate that overexpression of CuZnSOD in coronary vascular cells renders the heart more resistant to I/R injury. (C) 2000 Elsevier Science Inc.