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L-谷氨酸和谷氨酰胺可改善血流动力学功能并在缺血后再灌注期间恢复心肌糖原含量:大鼠离体心脏的放射性示踪研究

L-glutamate and glutamine improve haemodynamic function and restore myocardial glycogen content during postischaemic reperfusion: A radioactive tracer study in the rat isolated heart.

作者信息

Støttrup Nicolaj B, Kristiansen Steen B, Løfgren Bo, Hansen Bo Falck, Kimose Hans-Henrik, Bøtker Hans Erik, Nielsen Torsten Toftegaard

机构信息

Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Clin Exp Pharmacol Physiol. 2006 Nov;33(11):1099-103. doi: 10.1111/j.1440-1681.2006.04497.x.

Abstract
  1. L-Glutamate and glutamine have been suggested to have cardioprotective effects. However, the issue is controversial and the metabolic mechanisms underlying a beneficial effect are not well understood. 2. In the present study we investigated the effects of L-glutamate and glutamine on haemodynamic recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake during postischaemic reperfusion. 3. Hearts from male Wistar rats (250-300 g) were divided into three groups as follows: (i) control (n = 12); (ii) L-glutamate (n = 12); and (iii) glutamine (n = 12). Hearts were mounted in a Langendorff preparation and perfused with oxygenated Krebs'-Henseleit solution at 80 mmHg and 37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during which L-glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]-glucose and myocardial glucose uptake using D-[2-3H]-glucose were measured. 4. L-Glutamate and glutamine increased postischaemic LVDP (P < 0.01 vs control hearts for both). L-Glutamate and glutamine increased de novo glycogen synthesis by 78% (P < 0.001) and 55% (P < 0.01), respectively. At the end of reperfusion, total myocardial glycogen content was increased by both L-glutamate and glutamine (5.7 +/- 0.3 and 6.2 +/- 0.7 micromol/g wet weight, respectively; P < 0.05 and 0.01, respectively) compared with that in control hearts (3.6 +/- 0.4 micromol/g wet weight). Neither L-glutamate nor glutamine affected myocardial glucose uptake during reperfusion. 5. Improved postischaemic haemodynamic recovery after L-glutamate and glutamine supplementation during reperfusion is associated with increased de novo glycogen synthesis, suggesting a favourable modulation of intracellular myocardial carbohydrate metabolism.
摘要
  1. 已有研究表明L-谷氨酸和谷氨酰胺具有心脏保护作用。然而,这一问题存在争议,其有益作用背后的代谢机制尚未完全明确。2. 在本研究中,我们调查了L-谷氨酸和谷氨酰胺对缺血后再灌注期间血流动力学恢复、糖原从头合成速率以及心肌葡萄糖摄取的影响。3. 将雄性Wistar大鼠(250 - 300克)的心脏分为三组:(i)对照组(n = 12);(ii)L-谷氨酸组(n = 12);(iii)谷氨酰胺组(n = 12)。将心脏安装在Langendorff装置中,在80 mmHg和37℃下用含氧的Krebs'-Henseleit溶液灌注。先进行20分钟的全心缺血,随后进行15分钟的再灌注,在此期间给予L-谷氨酸(50 mmol/L)或谷氨酰胺(20 mmol/L)。测量左心室舒张末压(LVDP)、使用[14C]-葡萄糖进行糖原的从头合成以及使用D-[2-3H]-葡萄糖进行心肌葡萄糖摄取。4. L-谷氨酸和谷氨酰胺均增加了缺血后的LVDP(两者与对照组心脏相比,P < 0.01)。L-谷氨酸和谷氨酰胺分别使糖原从头合成增加了78%(P < 0.001)和55%(P < 0.01)。再灌注结束时,与对照组心脏(3.6 ± 0.4微摩尔/克湿重)相比,L-谷氨酸和谷氨酰胺均增加了心肌总糖原含量(分别为5.7 ± 0.3和6.2 ± 0.7微摩尔/克湿重;P分别 < 0.05和0.01)。L-谷氨酸和谷氨酰胺在再灌注期间均未影响心肌葡萄糖摄取。5. 再灌注期间补充L-谷氨酸和谷氨酰胺后缺血后血流动力学恢复的改善与糖原从头合成增加有关,提示对细胞内心肌碳水化合物代谢有有利调节作用。

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