小剂量地塞米松对生长期小鼠骨微结构及骨代谢的影响

摘要

目的：观察小剂量地塞米松对生长期小鼠骨微结构及骨代谢的影响。方法24只4周龄雌性小鼠随机分两组（ n＝12）：地塞米松组（DEX，1 mg／kg，肌肉注射，2次／周），对照组。4 w后处死小鼠，检测血清Ⅰ型前胶原N端肽（PINP）和骨Ⅰ型胶原交联C端肽（β⁃CTX）蛋白的表达水平；检测胫骨干骺端骨保护素（ OPG）、核因子⁃κ B受体活化因子配体（ RANKL）表达；抗酒石酸酸性磷酸酶（ TRAP）染色方法检测破骨细胞；一侧胫骨行显微CT扫描分析。结果 DEX组小鼠胫表观骨密度和骨体积分数明显高于对照组（P＜0�05），骨小梁数量高于对照组，结构模型指数低于对照组，但无统计学意义。 DEX组小鼠血清PINP及β⁃CTX浓度显著下降（P＜0�05）。 DEX组小鼠胫骨干骺端OPG表达明显增多，而RANKL表达无明显变化，相对于对照组，OPG／RANKL比值升高。 TRAP染色示DEX组小鼠胫骨干骺端破骨细胞数量较对照组减少。结论小剂量地塞米松间断给药可能通过上调OPG／RANKL比率维持生长期小鼠骨量。%Objective To observe the effects of low⁃dose dexamethesone on bone microachitecture and metabolism in growing period mice. Methods Twenty⁃four 4⁃week⁃old female mice were randomLy assigned to two groups ( n=12 ): Dexamethesone group (DEX, 1mg/kg, intramuscularly injected, twice/w); and the control group. 4 weeks after treatment, all the mice were sacrificed Serum aminoterminal propeptide of type I procollagen ( PINP) and carboxy⁃terminal telopeptide of type I collagen ( CTX) were measured by enzyme linked immunoabsorbent assay ( ELISA ) . OPG and RANKL of metaphyseal were detected by immunohistochemistry analysis. One tibia of each mouse was selected for microCT analysis. Results Trabecular aBMD and bone volume fraction of the femur significantly increased in DEX group than that of the control group(P<0�05). Trabecular number and structure model index increased in the DEX group, while there was no significant difference between two groups. In contrast to th control mice, serum PINP and CTX significantly decreased in DEX mice ( P < 0�05 ) OPG expression in tibia metaphyseal significantly increased in DEX mice, but there was no significant change in RANKL expression. And OPG/RANKL ratio significantly increased in DEX mice. In contrast to the control mice, the number of osteoclasts of tibia metaphyseal in DEX mice decreased. Conclusion Intermittent administration of low⁃dose dexamethasone may maintain bone mass in growing mice by upregulating OPG/RANKL ratio.