Chen Z, Oberley T D, Ho Y, Chua C C, Siu B, Hamdy R C, Epstein C J, Chua B H
The Cecile Cox Quillen Laboratory of Geriatrics, James H. Quillen School of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Free Radic Biol Med. 2000 Oct 1;29(7):589-96. doi: 10.1016/s0891-5849(00)00363-4.
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.
超氧化物歧化酶可清除氧自由基，而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适度增加铜/锌超氧化物歧化酶（CuZnSOD）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CuZnSOD mRNA，在转基因小鼠心脏中检测到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，转基因小鼠心脏的内皮细胞和平滑肌细胞胞质部分中CuZnSOD的标记增加，但心肌细胞中没有增加。当这些心脏在全心缺血35分钟后作为Langendorff标本灌注45分钟时，以心率×左心室舒张末压表示的心脏功能恢复在转基因心脏中为48±3%，而在非转基因心脏中为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著减少。我们的结果表明，冠状动脉血管细胞中CuZnSOD的过表达使心脏对I/R损伤更具抵抗力。
