Single dose of glutamine enhances myocardial tissue metabolism, glutathione content, and improves myocardial function after ischemia-reperfusion injury
Single dose of glutamine enhances myocardial tissue metabolism, glutathione content, and improves myocardial function after ischemia-reperfusion injury
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DOI：
10.1177/0148607103027006396
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发表时间：
2003-11-01
影响因子：
3.4
通讯作者：
Serkova, N
中科院分区：
文献类型：
--
作者：
Wischmeyer, PE;Jayakar, D;Serkova, N
背景：心肌缺血再灌注（I/R）损伤的发病率和死亡率很高。对I/R损伤的保护可能通过保存组织代谢和ATP含量、保存还原型谷胱甘肽和刺激热休克蛋白（HSP）合成来实现。据报道，补充谷氨酰胺（GLN）对所有这些保护途径都有有益的作用。因此，我们假设在体内给予大鼠GLN预处理可以保护心肌免受I/ r诱导的功能障碍。方法：在Sprague-Dawley大鼠心脏切除、灌注、全脑缺血（15分钟）和再灌注（1小时）前18小时给予GLN （0.52 g/kg，腹腔注射，以丙氨酸-谷氨酰胺二肽形式给予）、丙氨酸单独（0.23 g/kg）或乳酸林格氏液（对照）。组织代谢产物通过磁共振波谱分析。结果：在对照组和丙氨酸处理的动物中，I/R损伤导致心功能障碍，表现为心输出量减少。I/R损伤前18小时给予GLN可保护再灌注后的心输出量。心肌组织代谢分析显示，I/R损伤导致对照动物心肌组织谷氨酸、ATP含量、心肌乳酸积累和还原性谷胱甘肽含量显著降低。GLN显著降低心肌代谢的有害变化，提高还原性谷胱甘肽含量。注射GLN后，i /R损伤前后HSP表达均无变化。结论：这些观察结果表明，心脏I/R损伤前远程体内给药GLN可以改善I/R后心功能。这种作用可能是通过改善心肌代谢和增加还原性谷胱甘肽含量介导的。
Background: Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Protection against I/R injury may occur via preservation of tissue metabolism and ATP content, preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis. Supplementation with glutamine (GLN) has been reported to have beneficial effects on all of these protective pathways. Thus, we hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced dysfunction. Methods: GLN (0.52 g/kg, intraperitoneally, given as alanine-glutamine dipeptide), alanine alone (0.23 g/kg), or a Ringer's lactate solution (control) was administered to Sprague-Dawley rats 18 hours before heart excision, perfusion, exposure to global ischemia (15 minutes) and reperfusion (1 hour). Tissue metabolites were analyzed via magnetic resonance spectroscopy. Results: In control and alanine-treated animals, I/R injury resulted in cardiac dysfunction, indicated by a decrease in cardiac output. Administration of GLN 18 hours before I/R injury preserved cardiac output after reperfusion. Metabolic analysis of the myocardial tissue revealed that I/R injury led to significant diminution of myocardial tissue glutamate, ATP content, accumulation of myocardial lactate, and a reduction in reduced glutathione content in control animals. GLN significantly reduced the deleterious changes in myocardial metabolism and improved reduced glutathione content. No changes in pre- or post-I/R injury HSP expression were observed after GLN administration. Conclusions: These observations demonstrate that remote in vivo administration of GLN before cardiac I/R injury can improve post-I/R cardiac function. This effect may be mediated via improved myocardial metabolism and enhanced reduced glutathione content.