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目的比较近交系和封闭群Wistar大鼠对地塞米松(dexamethasone,Dex)诱导骨骼肌萎缩的药物效应,探讨建立大鼠糖皮质激素性骨骼肌萎缩症(glucocorticoid-induced muscular atrophy,GIMA)模型的优选方案。方法两品系大鼠各32只采用数字表法随机分为4组:对照组(C组)肌肉注射0.9%氯化钠注射液1.0 m L/kg,每周3次;低频组(L组)、中频组(M组)和高频组(H组)分别每周1、3、5次肌肉注射Dex 1.0 mg/kg,给药90 d,取腓肠肌进行形态学及糖皮质激素受体(glucocorticoid receptors,GR)和肌肉萎缩盒F蛋白(muscle atrophy F-box,MAFbx)基因mRNA表达水平检测。结果 (1)两品系大鼠H组的体质量[近交系:(158.4±7.3)g,封闭群:(196.5±14.4)g]较对照组[近交系:(223.7±10.5)g,封闭群:(279.5±14.5)g]显著减小;两品系大鼠H组的腓肠肌系数变化率[近交系:(-10.90±0.07)%,封闭群:(-13.60±0.12)%]较对照组[近交系:(±0.05)%,封闭群:(±0.01)%]显著减小;M、H组肌纤维横截面积变化率[近交系M和H组:(-13.00±2.00)%、(-29.00±2.00)%,封闭群M和H组:(-31.00±2.00)%、(-35.00±2.00)%较对照组近交系:(±3.40)%,封闭群:(±2.30%)]显著减小;用药组Ⅱ型纤维横截面积变化率[近交系L、M和H组:(-18.00±2.00)%、(-25.00±3.00)%、(-38.00±2.00)%,封闭群L、M和H组:(-45.00±1.00)%、(-53.00±1.00)%、(-44.00±2.00)%较对照组近交系:(±3.00)%,封闭群:(±3.00)%]显著减少。随给药频次增加,近交系大鼠Ⅱ型纤维横截面积变化率减少且组间差异有统计学意义(P<0.05)。(2)两品系大鼠各给药组MAFbx mRNA表达变化率[近交系L、M、H组:(175.00±10.00)%、(675.00±25.00)%、(2 125.00±25.00)%,封闭群L、M、H组:(15.00±2.00)%、(21.00±6.00)%、(33.00±3.00)%]均随给药频次增加而显著增高且组间差异有统计学意义(P<0.05)。近交系大鼠M组GR mRNA表达变化率(400.00±25.00)%和H组GR mRNA表达变化率(750.00±37.00)%较对照组(±37.00)%显著增高,但封闭群大鼠M组GR mRNA表达变化率(-26.00±5.00)%和H组GR mRNA表达变化率(-55.00±6.00)%较对照组(±2.00)%显著下降。结论以Dex 1.0 mg/kg每周1、3、5次肌肉注射均能诱导两品系大鼠不同程度的骨骼肌萎缩病变,但近交系大鼠较封闭群大鼠骨骼肌萎缩病变更为典型。
Objective To compare the drug effects of dexamethasone (Dex) -induced skeletal muscle atrophy in inbred and confinement Wistar rats and to establish a model of rat glucocorticoid-induced muscular atrophy (GIMA) The preferred solution. Methods Thirty-two rats in each of the two strains were randomly divided into four groups according to the digital table method: 0.9% sodium chloride injection 1.0 m L / kg intramuscularly in control group (C group) (M group) and high frequency group (H group) were injected intramuscularly with Dex 1.0 mg / kg for 1 week, 3 and 5 times respectively for 90 days. The gastrocnemius muscle was taken for morphology and glucocorticoid receptor receptors, GR) and muscle atrophy F-box (MAFbx) gene mRNA expression levels were detected. RESULTS: The body weight (inbred line: (158.4 ± 7.3) g, closed group: (196.5 ± 14.4) g] in the two groups of rats compared with the control group [inbred line: (223.7 ± 10.5) g, (279.5 ± 14.5) g] in the two groups were significantly lower than those in the control group (P <0.05). The rate of change of gastrocnemius coefficient in two groups of rats was significantly higher than that in the control group [inbred line: (-10.90 ± 0.07)%, (-13.60 ± 0.12)%] In the control group [(± 0.05)% in the inbred line, (± 0.01)% in the blocking group), the changes in the cross-sectional area of myofibers in M and H groups ) And (-29.00 ± 2.00)%, respectively, in the M and H closure groups: (- 31.00 ± 2.00)% and (-35.00 ± 2.00)%, ± 2.30%, respectively]). The rate of change of cross-sectional area of type Ⅱ fibers in the treatment group [(-18.00 ± 2.00)%, (-25.00 ± 3.00)%, (-38.00 ± (± 3.00)% of the inbred lines of the control group, (± 45% ± 1.00)%, (± 53.00 ± 1.00)%, and Group: (± 3.00)%] Significantly reduced. With the increase of frequency of administration, the rate of change of type Ⅱ fiber cross-sectional area in inbred rats decreased, and the difference between the two groups was statistically significant (P <0.05). (2) The rate of change of MAFbx mRNA expression in each group of two strains of rats [(175.00 ± 10.00)%, (675.00 ± 25.00)%, (2 125.00 ± 25.00)%, L (15.00 ± 2.00)%, (21.00 ± 6.00)%, (33.00 ± 3.00)%] in group L, M and H increased significantly with the increase of frequency of administration, and the difference between groups was statistically significant (P <0.05 ). The rate of change of GR mRNA expression was (400.00 ± 25.00)% in M group and 750.00 ± 37.00% in H group were significantly higher than that in control group (M ± 37.00)%, but M group The change rate of GR mRNA expression was (-26.00 ± 5.00)% and that of H group (-55.00 ± 6.00)% was significantly lower than that of control group (± 2.00)%. Conclusion Dextrine at a dose of 1.0 mg / kg per week can induce skeletal muscle atrophy in rats of two different grades, but the skeletal muscle atrophy is more typical in inbred rats than in closed rats .