摘要
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.
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） % , （ -
作者
翟玉莹
李青南
刘洋
林晓文
叶小天
陈珺
卢丽
杨国柱
陆幸妍
ZHAI Yu-ying LI Qing-nan LIU Yang LIN Xiao-wen YE Xiao-tian CHEN Jun LU Li YANG Guo-zhu LU Xing-yan(School of Life Science and Biopharmacy, Guangdong Pharmaceutical University/Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, Guangzhou 510006, China Guangdong Laboratory Animal Monitoring lnstitute/Guangdong Key Laboratory of Laboratory Animal, Guangzhou 510633, China)
出处
《中华骨质疏松和骨矿盐疾病杂志》
CSCD
2017年第1期58-65,共8页
Chinese Journal Of Osteoporosis And Bone Mineral Research
基金
广东省科技计划项目(2013B06030002)
