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低剂量甲泼尼龙和地夫可特治疗对大鼠膈肌收缩力和组织病理学的影响不同。

Rat diaphragm contractility and histopathology are affected differently by low dose treatment with methylprednisolone and deflazacort.

作者信息

Dekhuijzen P N, Gayan-Ramirez G, Bisschop A, de Bock V, Dom R, Bouillon R, Decramer M

机构信息

Respiratory Muscle Research Unit, University Hospital, Katholieke Universiteit Leuven, Belgium.

出版信息

Eur Respir J. 1995 May;8(5):824-30.

PMID:7656957
Abstract

The extent to which treatment with low doses of the nonfluorinated steroid methylprednisolone affects diaphragm contractility and morphology is unknown. In the present study, we compared the effects of equipotent doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism. Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg.kg-1 or deflazacort 0.5 mg.kg-1 i.m. Contractile properties and histopathology were measured after a 6 week treatment period. During treatment, body weight increased in control and methylprednisolone-treated animals, but decreased by 4.2 +/- 1.1% (mean +/- SD) in the deflazacort group. Similarly, diaphragm mass in the deflazacort group was decreased compared to control and methylprednisolone groups. Twitch tension and twitch characteristics of isolated diaphragm bundles were similar in the three groups. Maximal tetanic tension was decreased in the deflazacort group. The force-frequency curve of the deflazacort bundles shifted downwards compared to control. Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals. Microscopic examination revealed no gross abnormalities in the three groups. Histochemical analysis after staining for myosin adenosine triphosphatase (ATP-ase) showed that in the deflazacort group cross-sectional area of type I, IIa and IIb fibres were decreased. We conclude that low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimensions, while deflazacort at an equipotent dose induced generalized fibre atrophy and changes in diaphragm contractility.

摘要

低剂量非氟化类固醇甲泼尼龙治疗对膈肌收缩力和形态的影响程度尚不清楚。在本研究中,我们比较了等效剂量的甲泼尼龙和地夫可特(泼尼松龙的恶唑啉衍生物,对骨骼结构和碳水化合物代谢的全身副作用较小)的作用。26只成年雄性大鼠被随机分为三组,分别每日肌肉注射生理盐水(对照组)、0.4mg·kg-1甲泼尼龙或0.5mg·kg-1地夫可特。在6周的治疗期后测量收缩特性和组织病理学。治疗期间,对照组和甲泼尼龙治疗组的体重增加,而地夫可特组体重下降了4.2±1.1%(平均值±标准差)。同样,与对照组和甲泼尼龙组相比,地夫可特组的膈肌质量降低。三组中分离的膈肌束的单收缩张力和单收缩特性相似。地夫可特组的最大强直张力降低。与对照组相比,地夫可特组膈肌束的力-频率曲线向下移动。在此方案中,甲泼尼龙和地夫可特治疗的动物疲劳最严重。显微镜检查显示三组均无明显异常。肌球蛋白三磷酸腺苷酶(ATP酶)染色后的组织化学分析表明,地夫可特组I型、IIa型和IIb型纤维的横截面积减小。我们得出结论,低剂量甲泼尼龙对大鼠膈肌收缩特性产生细微且可忽略不计的变化,而不影响纤维尺寸,而等效剂量的地夫可特则导致广泛性纤维萎缩和膈肌收缩力改变。

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