McGuinness Jonathan, Neilan Tom G, Cummins Rob, Sharkasi Adel, Bouchier-Hayes David, Redmond J Mark
The Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin, Ireland.
J Surg Res. 2009 Mar;152(1):140-7. doi: 10.1016/j.jss.2008.03.045. Epub 2008 Apr 28.
Preconditioning, a highly evolutionary conserved endogenous protective response, provides the most powerful form of anti-infarct protection known. We investigated whether acute intravenous glutamine, through an effect on cyclooxygenase (COX)-2 and heat shock protein (HSP) 72, might induce preconditioning.
Male New Zealand white rabbits (n = 28) received either 0.5 g/kg glutamine in 0.9% saline or saline only in divided doses for 3 d. The large marginal branch of the left coronary was occluded for 30 min; cardiac function was assessed during 3 h of reperfusion, and infarct size was measured. 6-Keto-PGF-1alpha, nitrate, and malonaldehyde serum levels were determined. Hearts were taken from a further group of pretreated rabbits (n = 10) to assess myocardial COX-2 and HSP72 levels.
Glutamine pretreatment resulted in a 39% reduction in infarct size (30.7 +/- 2.0% versus 50.4 +/- 2.1% controls; P < 0.01). Myocardial COX-2 levels were significantly elevated with pretreatment (P < 0.05) and were mirrored by higher serum 6-keto-PGF-1alpha levels prior to ischemia (69 +/- 13 versus 18 +/- 21 pg/mL in controls, P = 0.027). There was no significant difference in myocardial HSP72 or serum nitrate levels following pretreatment, or malonaldehyde levels during reperfusion.
Glutamine pretreatment confers anti-infarct protection through up-regulation of COX-2, a key mediator of delayed preconditioning protection. Previous confirmation of its clinical safety profile at these doses suggests an acceptable strategy for inducing preconditioning for perioperative protection.
预处理是一种高度进化保守的内源性保护反应，是已知最强大的抗梗死保护形式。我们研究了急性静脉注射谷氨酰胺是否通过对环氧合酶（COX）-2和热休克蛋白（HSP）72的影响来诱导预处理。
28只雄性新西兰白兔，一组接受0.5g/kg谷氨酰胺溶于0.9%盐水中，另一组仅接受盐水，均分为3剂给药，共3天。结扎左冠状动脉大边缘支30分钟；在再灌注3小时期间评估心功能，并测量梗死面积。测定血清6-酮-前列腺素F1α、硝酸盐和丙二醛水平。从另一组预处理兔（n = 10）中取出心脏，评估心肌COX-2和HSP72水平。
谷氨酰胺预处理使梗死面积减少39%（30.7±2.0%对对照组50.4±2.1%；P < 0.01）。预处理后心肌COX-2水平显著升高（P < 0.05），缺血前血清6-酮-前列腺素F1α水平升高与之相符（对照组为18±21 pg/mL，预处理组为69±13 pg/mL，P = 0.027）。预处理后心肌HSP72或血清硝酸盐水平以及再灌注期间丙二醛水平无显著差异。
谷氨酰胺预处理通过上调COX-2赋予抗梗死保护作用，COX-2是延迟预处理保护的关键介质。此前对这些剂量下其临床安全性的确认表明，这是一种可接受的诱导预处理以实现围手术期保护的策略。
