Van Balkom R H, Dekhuijzen P N, Folgering H T, Veerkamp J H, Van Moerkerk H T, Fransen J A, Van Herwaarden C L
Department of Pulmonary Diseases, University Hospital Nijmegen, University of Nijmegen, The Netherlands.
J Appl Physiol (1985). 1998 May;84(5):1492-9. doi: 10.1152/jappl.1998.84.5.1492.
Animal and clinical studies have shown respiratory muscle dysfunction caused by treatment with glucocorticoids. The present study was designed to investigate whether anabolic steroids are able to antagonize the loss of diaphragm force induced by long-term low-dose methylprednisolone (MP) administration. Male adult rats were randomized to receive saline or MP (0.2 mg . kg-1 .day-1 sc) during 9 mo, with or without nandrolone decanoate (ND; 1 mg . kg-1 . wm -1 im) during the last 3 mo. The approximately 10% reduction in force generation of isolated diaphragm bundles induced by MP was completely abolished by addition of ND. The MP-induced decrease in number of fibers expressing type IIb myosin heavy chains was not reversed by ND. MP slightly reduced type I, IIa, and IIx fiber cross-sectional areas (CSA), but not type IIb fiber CSA. Addition of ND abolished the reduction in IIa and IIx fiber CSA. The MP-induced alterations in glycogenolytic activity and fatty acid oxidation capacity were not reversed by ND. In conclusion, the marked reduction in diaphragm force caused by long-term low-dose MP was completely abolished by addition of ND. ND in part also antagonized the effects of MP on diaphragm morphology but showed no beneficial effects on biochemical changes.
动物和临床研究表明,糖皮质激素治疗可导致呼吸肌功能障碍。本研究旨在调查合成代谢类固醇是否能够对抗长期低剂量甲基强的松龙(MP)给药引起的膈肌力量丧失。成年雄性大鼠被随机分为两组,在9个月内分别接受生理盐水或MP(0.2mg·kg-1·天-1,皮下注射),在最后3个月内,一组加用癸酸诺龙(ND;1mg·kg-1·周-1,肌肉注射),另一组不加。MP诱导的离体膈肌束力量产生约10%的降低,通过添加ND可完全消除。ND不能逆转MP诱导的表达IIb型肌球蛋白重链的纤维数量减少。MP使I型、IIa型和IIx型纤维横截面积(CSA)略有减小,但对IIb型纤维CSA无影响。添加ND可消除IIa型和IIx型纤维CSA的减小。ND不能逆转MP诱导的糖原分解活性和脂肪酸氧化能力的改变。总之,长期低剂量MP引起的膈肌力量显著降低,通过添加ND可完全消除。ND部分拮抗了MP对膈肌形态的影响,但对生化变化无有益作用。