Kemp G J, Taylor D J, Dunn J F, Frostick S P, Radda G K
MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, UK.
J Neurol Sci. 1993 Jun;116(2):201-6. doi: 10.1016/0022-510x(93)90326-t.
Cytosolic pH and phosphorus metabolite ratios in skeletal muscle were measured by 31P magnetic resonance spectroscopy in patients with Duchenne muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) and in Duchenne/Becker carriers. In resting dystrophin-deficient muscle, there was a decrease in phosphocreatine (PCr) and increase in orthophosphate (Pi) relative to ATP, and an increase in calculated free [ADP]. Phosphomonester and phosphodiester were also increased relative to ATP. These changes were largest in DMD, smaller in BMD and small or absent in carriers. Cytosolic pH was increased substantially in DMD, moderately in BMD and slightly but significantly in gastrocnemius of carriers. Raised intracellular pH thus appears to be the most characteristic abnormality in dystrophin-deficient muscle. Responses to erobic exercise were studied in the forearm muscle flexor digitorum superficialis of carriers. PCr depletion during exercise was greater than normal but the fall in pH was disproportionately small, resulting in increased [ADP]. This is likely to result either from reduced anaerobic glycogenolysis to lactic acid or from increased proton efflux (as is seen in mitochondrial myopathy). Detailed analysis suggests: (1) at the start of exercise, calculated lactic acid production was increased, as was the rate of PCr depletion, suggesting that there was no absolute defect of glycogenolysis. (2) At the start of recovery, calculated proton efflux was not increased, although as the pH at the end of exercise was higher than in controls and proton efflux is normally pH-dependent, an up-regulation of proton efflux cannot be excluded. (3) Recovery of PCr, Pi and ADP after exercise were not impaired, suggesting that mitochondrial function is normal.
采用31P磁共振波谱法测量了杜氏肌营养不良症（DMD）、贝克氏肌营养不良症（BMD）患者及Duchenne/Becker携带者骨骼肌的胞质pH值和磷代谢物比率。在静息的肌营养不良蛋白缺乏的肌肉中，相对于三磷酸腺苷（ATP），磷酸肌酸（PCr）减少，正磷酸盐（Pi）增加，计算得出的游离[二磷酸腺苷（ADP）]增加。相对于ATP，磷酸单酯和磷酸二酯也增加。这些变化在DMD中最大，在BMD中较小，在携带者中则很小或没有变化。DMD患者的胞质pH值大幅升高，BMD患者中度升高，携带者腓肠肌轻度但显著升高。因此，细胞内pH值升高似乎是肌营养不良蛋白缺乏肌肉中最具特征性的异常。对携带者的前臂肌肉指浅屈肌进行了有氧运动反应研究。运动期间PCr消耗比正常情况更大，但pH值下降幅度不成比例地小，导致[ADP]增加。这可能是由于无氧糖原分解为乳酸减少或质子外流增加（如线粒体肌病所见）所致。详细分析表明：（1）运动开始时，计算得出的乳酸生成增加，PCr消耗速率也增加，表明糖原分解没有绝对缺陷。（2）恢复开始时，尽管运动结束时的pH值高于对照组，且质子外流通常依赖于pH值，但计算得出的质子外流没有增加，不能排除质子外流上调的可能性。（3）运动后PCr、Pi和ADP的恢复没有受损，表明线粒体功能正常。
