Majumdar R, Cwik V A, Solonynko G, Brooke M H
Department of Medicine, Heritage Medical Research Centre, University of Alberta, Edmonton, Canada.
Acta Physiol Scand. 1993 Nov;149(3):249-55. doi: 10.1111/j.1748-1716.1993.tb09620.x.
The efflux of hypoxanthine and uric acid from skeletal muscle has been noted to follow exercise and metabolic stress both in vivo and in vitro. Since the action of xanthine oxidase and hypoxanthine generates free radicals with potential damaging effect on the muscle membranes, an in vitro model was used to study the relationship of metabolic stress, oxypurine release and muscle contraction. When rat epitrochlearis muscle was exposed to the mitochondrial uncoupler dinitrophenol at 37 degrees C, lactate release was pronounced and hypoxanthine and uric acid appeared in the incubating medium. The twitch tension, in response to supramaximal stimulation, was reduced to less than 5% of the initial value. When the same experiment was repeated at 27 degrees C, hypoxanthine and uric acid formation was inhibited, although lactate release indicated that metabolic stress was still present. Twitch tension was relatively preserved (57% of the initial value). The lower temperature did not alter the decrease in ATP and phosphocreatine levels in the muscle which is produced by dinitrophenol. There was an inverse relationship between oxypurine release and twitch tension in individual muscles (r = 0.80, P < 0.01 for hypoxanthine and r = 0.95, P < 0.0002 for uric acid). Xanthine dehydrogenase/xanthine oxidase was detected in muscle and between 16 and 22% of the activity was in the oxidase form.
体内和体外实验均已表明，骨骼肌中次黄嘌呤和尿酸的外流与运动及代谢应激有关。由于黄嘌呤氧化酶作用于次黄嘌呤会产生自由基，可能对肌膜造成潜在损害，因此采用体外模型来研究代谢应激、氧嘌呤释放与肌肉收缩之间的关系。当大鼠肱三头肌在37℃下暴露于线粒体解偶联剂二硝基苯酚时，乳酸释放明显，且孵育培养基中出现次黄嘌呤和尿酸。对超强刺激产生的抽搐张力降至初始值的5%以下。当在27℃重复相同实验时，次黄嘌呤和尿酸的形成受到抑制，尽管乳酸释放表明代谢应激仍然存在。抽搐张力相对得以保留（为初始值的57%）。较低温度并未改变二硝基苯酚引起的肌肉中ATP和磷酸肌酸水平的降低。在单个肌肉中，氧嘌呤释放与抽搐张力呈负相关（次黄嘌呤的r = 0.80，P < 0.01；尿酸的r = 0.95，P < 0.0002）。在肌肉中检测到黄嘌呤脱氢酶/黄嘌呤氧化酶，其中16%至22%的活性以氧化酶形式存在。
