【摘要】 目的 基于Wnt/β-联蛋白（β-catenin）信号通路探讨坚骨胶囊对骨质疏松症模型大鼠的作用及机制。方法 将50只Wistar雌性大鼠随机分为正常对照组，模型对照组，坚骨胶囊高、中、低剂量组[2 184,1 092,546 mg/（kg·d）]，各10只。除正常对照组外，其余各组大鼠均灌胃100 mg/kg维甲酸复制骨质疏松症模型，每天1次，连续30 d。坚骨胶囊高、中、低剂量组大鼠灌胃相应剂量药物，正常对照组和模型对照组大鼠均灌胃纯化水8 mL/kg，每天1次，连续30 d。检测各组大鼠血清的生化指标Ca2+、Mg2+、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）、碱性磷酸酶（ALP）水平；利用Micro-CT仪记录骨微结构，并检测大鼠股骨微结构指标[远心端感兴趣区结构模型指数（SMI）、骨密度（BMD）、骨体积分数（BV/TV）、骨表面与骨体积比（BS/BV）、骨小梁数量（TbN）、骨小梁厚度（TbTh）、骨小梁分离度（TbSp）]；采用免疫印迹（Western blot）法检测股骨组织中细胞周期蛋白D1(CyclinD1)、β-catenin、低密度脂蛋白受体相关蛋白5(LRP5)、淋巴增强因子（LEF）的蛋白表达水平。结果 MicroCT仪检测结果显示，坚骨胶囊高剂量组大鼠骨小梁结构最完整，与正常对照组股骨远心端骨小梁多呈板状、致密均匀接近。与模型对照组比较，坚骨胶囊中、高剂量组大鼠血清中MDA,GSH-Px,SOD水平均明显升高（P <0.05）,ALP水平均明显降低（P <0.05）；坚骨胶囊高剂量组大鼠股骨微结构中BMD,BV/TV,BS/BV,TbN,TbTh均明显升高，SMI和TbSp均明显降低（P <0.05）；坚骨胶囊高剂量组大鼠股骨组织中LRP5,β-catenin,LEF,CyclinD1蛋白表达均明显上调（P <0.05）。结论 坚骨胶囊能预防维甲酸诱导的大鼠骨质疏松，其作用机制可能与激活Wnt/β-catenin信号通路及其基因蛋白表达有关。更多还原

【Abstract】 ObjectiveTo investigate the effect and mechanism of Jiangu Capsules on the osteoporosis model rats based on the Wnt/β-catenin signaling pathway.MethodsA total of 50 female Wistar rats were randomly divided into the normal control group,the model control group,the Jiangu Capsules high-,medium-and low-dose groups [2 184,1 092,546 mg/（kg · d）],with 10 rats in each group. Except for the normal control group,the rats in the other groups were given 100 mg/kg of tretinoin by gavage to replicate the osteoporosis model,once a day,for 30 d. The rats in the Jiangu Capsules high-,medium-and low-dose groups were given corresponding doses of drugs by gavage,and the rats in the normal control group and the model control group were given 8 mL/kg of purified water by gavage,once a day,for 30 d. The levels of serum biochemical indexes Ca2+,Mg2+,malondialdehyde(MDA),glutathione peroxidase(GSH-Px),total antioxidant capacity(T-AOC),superoxide dismutase(SOD) and alkaline phosphatase(ALP) in each group were detected. The Micro-CT was used to record the femoral microstructure and detect the related indexes [structural model index(SMI),bone mineral density(BMD),bone volume/total volume(BV/TV),bone surface/bone volume(BS/BV),trabecular number(TbN),trabecular thickness(TbTh),trabecular separation(TbSp) at distal region of interest]. The Western blot was used to detect the expression levels of CyclinD1,β-catenin,low-density lipoprotein receptor-related protein 5(LRP5) and lymphoid enhancing factor(LEF).Results structure was the most complete,and the trabecular at the distal end of the femur in the Jiangu Capsules high-dose group was mostly plate-like,dense and uniform,which was similar to that in the normal control group. Compared with those in the model control group,the levels of MDA,GSH-Px and SOD in serum of rats in the Jiangu Capsules medium-and high-dose groups were significantly higher(P < 0. 05),the ALP level in the Jiangu Capsules medium-and high-dose groups was significantly lower(P < 0. 05). Compared with those in the model control group,BMD,BV/TV,BS/BV,TbN and TbTh in the femoral microstructure of rats in the Jiangu Capsules high-dose group were significantly higher,while SMI and TbSp in the Jiangu Capsules high-dose group were significantly lower(P < 0. 05). Compared with those in the model control group,the expression levels of LRP5,β-catenin,LEF and CyclinD1 proteins in femoral tissue of rats in the Jiangu Capsules high-dose group were significantly higher(P < 0. 05).Conclusion mechanism may be related to the activation of Wnt/β-catenin signaling pathway and the expression of related proteins.更多还原