地塞米松诱导近交系和封闭群Wistar大鼠骨骼肌萎缩效应比较

Comparison of the effects of dexamethasone inducing skeletal muscle atrophy in Wistar inbred and closed group rats

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 effects of dexamethasone （Dex） inducing skeletal muscle atrophy in in- bred and closed Wistar rats exploring the establishment of glucocorticoid induced skeletal muscle atrophy （ GIMA ） for the rats model. Methods The two strains of rats, 32 rats each, were randomly divided into 4 groups ： control （C） group were injected with saline 1 mL/kg, 3 times a week; low frequency （L） group, medium frequency （M） group and high frequency （H） group were 1, 3, 5 times weekly intramuscularly injected Dex 1 mg/kg for 90 days, gastrocnemius muscle was got for morphological observation and glucocorticoid receptor （GR） and muscle ring finger protein （MAFbx） gene expression level detection. Results （ 1 ） Compared with the control group [ inbred group： （223.7 ±10. 5 ） g, closed group： （ 279. 5 ± 14. 5） g], body mass of the H group of two strain rats [inbred group： （ 158. 4 ±7. 3） g, closed group： （ 196. 5 ± 14. 4） g] was significantly decreased. Compared with the control group [inbred group： （ -0. 05）%, closed group： （ -0. 01 ）% ], change rate of the gastrocnemius coefficient of the two strains rats in H group [ inbred group ： （ - 10. 90 ± 0. 07 ） %, closed group： （ -13.60±0. 12）% ] was significantly decreased. Compared with the control group [inbred group： （ -3.40）%, closed group： （ -2. 30）% ], muscle fiber cross-sectional area change rate in M and H group [ M and H group of inbred group： （-13.00±2.0）%, （ -29.00±2）%; M and H group of closed group： （ -31.00±2.00）%, （ -35.00± 2. 00）% ] was significantly decreased. Compared with the control group [ inbred group： （ - 3.00 ）%, closed group： （ ± 3.00） % , type Ⅱ fiber cross-sectional area change rate of administration groups [ L, M and H group of inbred group ： （ -18.00±2.00）%, （ -25.00±3.00）%, （ -38.00＋2.00）%; L, M and H group of closed group： （ -45.00± 1.00） % , （ - 53.00 ± 1.00） % , （ - 44. 00 ± 2. 00 ） % ] was decreased significantly. With the increase of the frequency of administration, there was a significant difference in the change rate of the cross-sectional area of the type Ⅱ fiber in the inbred strain rats （ P 〈 0. 05 ）. （2） With the increase of the frequency of administration, the change rate of expression of MAFbx mRNA in the two strains of rats [ L, M and H group of inbred group： （175.00 ± 10.00）%, （675.00± 25.00）%, （2 125.00 ±25.00）%; L, M and H group of closed group： （15.00 ±2.00）%, （21.00 ±6.00）%, （ 33.00 ±3.00 ） % ] were significantly increased. Compared with the control group （ ±37.00） % , the expression of GR mRNA in M group （400. 00 ±25.00 ） % and H group （ 750. 00 ±37.00） % of inbred group rats were significantly higher. But the expression of GR mRNA in M group （ - 26. 00 ± 5.00 ） % and H group （ - 55.00±6. 00） % of closed group rats decreased significantly than the control group （ ± 2. 00 ） %. Conclusion Dex at a dose of 1 mg/kg 1, 3, 5 times a week by intramuscular injection can induce two strains of rats with different degrees of skeletal muscle atrophy lesions, but compared with closed rats, inbred rat skeletal muscle atrophy was more typical.