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 analyze the correlation between epithelial sodium channel (ENaC) protein expression and skeletal muscle atrophy on the base of steroids muscle atrophy (SMA) SD rat model,and to explore the possible effect of ENaC in the path- ogenesis of SMA. Methods Thirty-two female SD rats aged 3 months were randomly divided into four groups: normal control group (C group,0.9% NaCI,4 times a week) ,treatment groups including low frequency group (L group) ,medium frequency group (M group) and high frequency group (H group). Dexamethasone (Dex) of 1 mg/kg was injected into the muscle,and the frequency of administration was, in order, 2 times, 4 times, 6 times a week. After 4 weeks, the rats were executed. The gastrocnemius were got for being weighed, being paraffin-embedded, HE staining,and morphological observed. FCSA was tested, α-ENaC and glucocorticoid receptor (GR) immunohistochemieal were analyzed. Results (1) The rat body weight and gastrocnemius wet weight decreased when compared to C group and between them there was a dose-dependent relationship. (2)Compared with C group,FCSA of treat- ment groups rats decreased,and between them there were dose dependent. (3)α-ENaC immunohistochemical analysis of gastrocne- mius showed that,compared with C group,the IOD values of L group, M group and H group rised. There was a dose-dependent re- lationship. GR immunohistochemical analysis showed that compared with C group,the IOD values of M group and H group rised. The IOD value change of α-ENaC and GR were positively correlated. Conclusion Increased expression of ENaC in skeletal muscle induced by GC,may be associated with steroid myopathy.