Enhancement of glutathione cardioprotection by ascorbic acid in myocardial reperfusion injury
Enhancement of glutathione cardioprotection by ascorbic acid in myocardial reperfusion injury
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抗坏血酸在心肌再灌注损伤中增强谷胱甘肽心脏保护作用。
DOI：
10.1124/jpet.301.2.543
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发表时间：
2002-05-01
影响因子：
3.5
通讯作者：
Ma, XL
中科院分区：
文献类型：
--
作者：
Gao, F;Yao, CL;Ma, XL
本实验测定了谷胱甘肽和抗坏血酸这两种最重要的亲水性抗氧化剂对心肌缺血再灌注损伤的影响，并评价了它们的相对治疗价值。离体大鼠心脏进行缺血（30分钟）和再灌注（120分钟）和治疗与抗坏血酸，谷胱甘肽单乙酯（GSHme），或其组合在再灌注开始。单独给予1 mM GSHme，而不是单独给予1 mM抗坏血酸，可显著减弱缺血后损伤（P，0.05，与溶媒相比）。最有趣的是，抗坏血酸与GSHme共同给药显著增强了GSHme的保护作用（与载体相比P < 0.01）。GSHme和抗坏血酸各以1 mM组合所发挥的保护作用显著大于单独使用1 mM GSHme所观察到的保护作用（P < 0.05）。此外，单独使用GSHme或GSHme加抗坏血酸治疗显着降低了心肌硝基酪氨酸水平，表明这些治疗减弱了心肌过氧亚硝酸盐的形成。这些结果表明，1）GSHme，而不是抗坏血酸，对缺血-再灌注损伤发挥保护作用;和2）GSHme的保护作用进一步增强，通过与抗坏血酸共同给药，表明GSHme和抗坏血酸之间的协同作用。
The present experiment determined the effects of glutathione and ascorbic acid, the two most important hydrophilic antioxidants, on myocardial ischemia-reperfusion injury and evaluated their relative therapeutic values. Isolated rat hearts were subjected to ischemia (30 min) and reperfusion (120 min) and treated with ascorbic acid, glutathione monoethyl ester (GSHme), or their combination at the onset of reperfusion. Administration of 1 mM GSHme alone, but not 1 mM ascorbic acid alone, significantly attenuated postischemic injury (P , 0.05 versus vehicle). Most interestingly, coadministration of ascorbic acid with GSHme markedly enhanced the protective effects of GSHme (P < 0.01 versus vehicle). The protection exerted by the combination of GSHme and ascorbic acid at 1 mM each was significantly greater than that observed with 1 mM GSHme alone (P < 0.05). Moreover, treatment with GSHme alone or GSHme plus ascorbic acid markedly reduced myocardial nitrotyrosine levels, suggesting that these treatments attenuated myocardial peroxynitrite formation. These results demonstrated that 1) GSHme, but not ascorbic acid, exerted protective effects against ischemia-reperfusion injury; and 2) the protective effects of GSHme were further enhanced by coadministration with ascorbic acid, suggesting a synergistic effect between GSHme and ascorbic acid.