Van Way Charles W, Dhar Animesh, Morrison David C, Longorio Mario A, Maxfield Daniel M
Department of Surgery, University of Missouri-Kansas City School of Medicine, USA.
J Trauma. 2003 May;54(5 Suppl):S169-76. doi: 10.1097/01.TA.0000047226.36678.EE.
This is a review of studies with two agents, glutamine and crocetin, which have been found to enhance recovery of cellular adenosine triphosphate (ATP) and adenosine diphosphate after hemorrhagic shock.
The studies used a sublethal (30 minutes) reservoir shock model in 300- to 350-g, male, Sprague-Dawley rats, using either ketamine-xylazine or isoflurane anesthesia. Glutamine was given as a 3% (21 mmol/L) solution in Ringer's lactate (630 mg/kg). Crocetin was given as a 500 nmol/L solution in Ringer's lactate (2 mg/kg).
Both glutamine and crocetin caused recovery of ATP to baseline levels (9.0 micromol/g) within 60 to 120 minutes after resuscitation. Xanthine levels returned more rapidly to baseline (0.1 micromol/g). Both agents prevented the elevation in apoptosis seen in controls at 24 and 48 hours.
Glutamine is a metabolic substrate and a precursor of ATP synthesis. Crocetin enhances oxygen diffusivity in plasma. Both agents restore cellular energy stores to normal after hemorrhagic shock and produce a marked diminution in the extent of apoptosis postshock. Their mechanism of action probably involves prevention of mitochondrial damage.
本文是对谷氨酰胺和藏红花素两种药物的研究综述,这两种药物已被发现可促进失血性休克后细胞三磷酸腺苷(ATP)和二磷酸腺苷的恢复。
研究采用亚致死性(30分钟)储血器休克模型,使用300至350克的雄性Sprague-Dawley大鼠,采用氯胺酮-赛拉嗪或异氟烷麻醉。谷氨酰胺以3%(21毫摩尔/升)的乳酸林格液溶液(630毫克/千克)给药。藏红花素以500纳摩尔/升的乳酸林格液溶液(2毫克/千克)给药。
谷氨酰胺和藏红花素均可使复苏后60至120分钟内ATP恢复至基线水平(9.0微摩尔/克)。黄嘌呤水平恢复至基线(0.1微摩尔/克)的速度更快。两种药物均能防止对照组在24小时和48小时出现的细胞凋亡增加。
谷氨酰胺是一种代谢底物,也是ATP合成的前体。藏红花素可提高血浆中的氧扩散率。两种药物均可使失血性休克后细胞能量储备恢复正常,并显著减少休克后细胞凋亡的程度。它们的作用机制可能涉及预防线粒体损伤。