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目的基于类固醇肌萎缩症(SMA)大鼠模型,分析大鼠骨骼肌萎缩与其上皮钠通道蛋白(ENaC)表达的相关性,探讨ENaC在SMA发病机制中的可能作用。方法将32只3个月龄雌性SD大鼠分为4组分别给药:对照组(C组)每周4次肌内注射生理盐水;低频给药组(L组)、中频给药组(M组)和高频给药(H组)分别予以每周2、4、6次肌内注射地塞米松(Dex)每次1.0mg/kg。给药4周停药处死,取腓肠肌称质量,石蜡包埋制片,行苏木精-伊红(HE)染色形态学观察,肌纤维横截面积(FCSA)测量,以及糖皮质激素受体(GR)和α-上皮钠通道蛋白(α-ENaC)免疫组织化学检测(IHC)及其相关性分析。结果 (1)各给药组大鼠体质量和腓肠肌湿质量均较C组下降,且有剂量依赖性。(2)各给药组FCSA均较C组减少,且有剂量依赖性。(3)GR的M和H组积分光密度(IOD)值较C组增高;α-ENaC的L、M和H组IOD值较C组增高,且有剂量依赖性;GR和α-ENaC的IOD值变化呈正相关。结论 GC诱导骨骼肌组织ENaC表达增高,可能与SMA的肌萎缩病变相关。
Objective To investigate the correlation between skeletal muscle atrophy and the expression of epithelial sodium channel protein (ENaC) in rat model of steroid-induced muscular atrophy (SMA) and to explore the possible role of ENaC in the pathogenesis of SMA. Methods 32 3-month-old female Sprague-Dawley rats were divided into four groups: control group (C), intramuscular injection of saline 4 times a week; low frequency group (L group), middle frequency group M group) and high-frequency group (H group) were administered intramuscularly with dexamethasone (Dex) at a dose of 1.0 mg / kg for 2, 4 and 6 times a week respectively. The rats were sacrificed after 4 weeks of treatment. Gastrocnemius muscle mass, paraffin-embedded tablets, HE staining, FCSA and glucocorticoid receptor ( GR) and α-epithelial sodium channel protein (α-ENaC) immunohistochemistry (IHC) and their correlation analysis. Results (1) The body weight and gastrocnemius wet weight of rats in each administration group were decreased compared with those in group C, and were dose-dependent. (2) The FCSA in each administration group was less than that in C group, and dose-dependent. (3) The integral optical density (IOD) values of M and H groups in GR group were higher than those in C group. The IOD values of L, M and H groups in α-ENaC group were higher than those in C group in a dose-dependent manner. GR and α-ENaC IOD changes were positively correlated. Conclusion GC induced increased expression of ENaC in skeletal muscle, which may be related to the muscle atrophy of SMA.