缺血性骨骼肌给予外源性三磷酸腺苷可诱导产生一种节能效应：涉及腺苷受体。
Administration of exogenous adenosine triphosphate to ischemic skeletal muscle induces an energy-sparing effect: role of adenosine receptors.
机构信息
Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky.
出版信息
J Surg Res. 2013 May 1;181(1):e15-22. doi: 10.1016/j.jss.2012.06.033. Epub 2012 Jul 6.
BACKGROUND
Ischemia-reperfusion injury is a devastating complication that occurs in allotransplantation and replantation of limbs. Over the years, several preservation strategies have been used to conserve the critical levels of intracellular adenosine triphosphate (ATP) during ischemia to sustain the ion gradients across the membranes and thus the tissue viability. The administration of exogenous ATP to ischemic tissues is known to provide beneficial effects during reperfusion, but it is unclear whether it provides protection during ischemia. The purpose of the present study was to determine the effect of ATP administration on high-energy phosphate levels in ischemic skeletal muscle and to examine the role of purinergic and adenosine receptors in mediating the response to exogenous ATP.
METHODS
The extensor digitorum longus muscles of Fischer rats were subjected to ischemia and treated with different concentrations of ATP with or without purinergic and adenosine receptor blockers. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to measure the rate of decay of ATP, phosphocreatine (PCr), and the formation of adenosine monophosphate and acidification. Phosphorylated compounds were analyzed using a simple model of energy metabolism, and the PCr half-life was used as an index of internal depletion of ATP to distinguish between intracellular and extracellular ATP.
RESULTS
PCr decay was rapid in all muscle groups and was followed by gradual ATP decay. The half-life of PCr was significantly longer in the ATP-treated muscles than in the vehicle controls and was maximally prolonged by treating with slow hydrolyzing adenosine 5'-O-(3-thio)triphosphate. Purinoceptor (P2X) blockade with ATP treatment significantly increased the half-life of PCr, and adenosine receptor blockers blunted the response. Administration of adenosine to ischemic muscles significantly increased the half-life of PCr compared with that in the vehicle controls.
CONCLUSIONS
Exogenous ATP administration to ischemic skeletal muscles appears to spare intracellular energy by acting primarily through adenosine receptors.
背景
缺血再灌注损伤是同种异体移植和肢体再植中发生的一种破坏性并发症。多年来，人们已经使用了几种保存策略来在缺血过程中保持细胞内三磷酸腺苷（ATP）的临界水平，以维持跨膜离子梯度，从而维持组织活力。已知向缺血组织中给予外源性 ATP 在再灌注期间会产生有益效果，但尚不清楚其在缺血期间是否具有保护作用。本研究的目的是确定 ATP 给药对缺血骨骼肌高能磷酸水平的影响，并研究嘌呤能和腺苷受体在介导对外源性 ATP 反应中的作用。
方法
费舍尔大鼠的趾长伸肌经历缺血，并接受不同浓度的 ATP 治疗，同时使用嘌呤能和腺苷受体阻滞剂。磷-31 核磁共振波谱用于测量 ATP、磷酸肌酸（PCr）的衰减率以及单磷酸腺苷和酸化的形成。使用简单的能量代谢模型分析磷酸化化合物，PCr 的半衰期被用作区分细胞内和细胞外 ATP 的内部 ATP 消耗的指标。
结果
所有肌肉群中的 PCr 衰减都很快，随后是逐渐的 ATP 衰减。在 ATP 处理的肌肉中，PCr 的半衰期明显长于载体对照，并且通过用缓慢水解的三磷酸腺苷 5'-O-(3-硫）处理可最大限度地延长。用 ATP 处理嘌呤能受体（P2X）阻滞剂可显著延长 PCr 的半衰期，而腺苷受体阻滞剂则减弱了该反应。与载体对照相比，向缺血肌肉中给予腺苷可显著增加 PCr 的半衰期。
结论
向缺血骨骼肌中给予外源性 ATP 似乎通过主要通过腺苷受体来节省细胞内能量。
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