Livingstone I, Johnson M A, Mastaglia F L
Neuropathol Appl Neurobiol. 1981 Sep-Oct;7(5):381-98. doi: 10.1111/j.1365-2990.1981.tb00240.x.
The extent to which dexamethasone treatment produced atrophy of fast-twitch (EDL) and slow-twitch (SOL) muscles in rat was investigated. The mean weight of steroid-treated EDL muscles was decreased as compared to normal, whereas SOL muscles from normal and dexamethasone-treated animals showed no significant difference. Muscle fibre diameters also showed comparatively minor changes in SOL, which consists of Type 1 (slow oxidative) and Type 2A (fast oxidative/glycolytic) fibres. Rat EDL contains, in addition to Type 1 and Type 2A fibres, two sub-populations of fast glycolytic fibres (Types 2B and 2B'). These fibre types showed the most severe degree of atrophy both after dexamethasone treatment and after denervation. The mean ratio of the weights of denervated to innervated EDL muscles was lower in steroid-treated rats than in normal animals suggesting that the atrophy produced by steroid treatment in conjunction with denervation was more than simply additive. Analysis of the proportions of histochemical fibre types in SOL and EDL showed that dexamethasone treatment produced no major alterations in the fibre type constitution of these muscles. However, further histochemical studies showed that there was relatively severe impairment of myophosphorylase activity in Type 2B' (fast glycolytic) fibres as compared to other fibre types; conversely Type 1 fibres frequently contained increased myophosphorylase. Levels of beta-hydroxybutyrate dehydrogenase were low in both normal and steroid-treated EDL but high in SOL which also showed higher general oxidative activity. It is suggested that the particular susceptibility of fast glycolytic fibres to atrophy as a result of steroid treatment may be linked to: 1 the relatively severe reduction of myophosphorylase activity in these fibres and 2 their comparative inability to utilize alternative energy sources, especially substrates derived from free fatty acids.
研究了地塞米松治疗对大鼠快肌(趾长伸肌,EDL)和慢肌(比目鱼肌,SOL)萎缩的影响程度。与正常大鼠相比,接受类固醇治疗的EDL肌肉平均重量下降,而正常大鼠和接受地塞米松治疗的大鼠的SOL肌肉重量无显著差异。SOL肌肉纤维直径变化相对较小,该肌肉由1型(慢氧化型)和2A型(快氧化/糖酵解型)纤维组成。大鼠EDL除了含有1型和2A型纤维外,还包含两个快速糖酵解纤维亚群(2B型和2B'型)。这些纤维类型在地塞米松治疗和去神经支配后均表现出最严重的萎缩程度。与正常动物相比,接受类固醇治疗的大鼠去神经支配的EDL与有神经支配的EDL肌肉重量平均比值更低,这表明类固醇治疗与去神经支配共同导致的萎缩不仅仅是简单的叠加。对SOL和EDL中组织化学纤维类型比例的分析表明,地塞米松治疗并未使这些肌肉的纤维类型构成发生重大改变。然而,进一步的组织化学研究表明,与其他纤维类型相比,2B'型(快速糖酵解型)纤维中的肌磷酸化酶活性相对严重受损;相反,1型纤维中的肌磷酸化酶活性常常增加。正常和接受类固醇治疗的EDL中β-羟丁酸脱氢酶水平均较低,而SOL中该酶水平较高,且SOL的总体氧化活性也较高。有人提出,快速糖酵解纤维因类固醇治疗而特别容易发生萎缩,可能与以下因素有关:1. 这些纤维中肌磷酸化酶活性相对严重降低;2. 它们相对无法利用替代能源,尤其是源自游离脂肪酸的底物。