牛膝-杜仲成分组合干预糖皮质激素性骨质疏松模型小鼠的研究
The study of Niuxi-Duzhong active mononer combination in preventing glucocorticoid-induced osteoporosis mice
  
DOI:10.3969/j.issn.1006-7108.2022.05.004
中文关键词:  糖皮质激素  骨质疏松  β-蜕皮甾酮  松脂醇二葡萄糖苷  骨强度
英文关键词:glucocorticoids  osteoporosis  β-Ecdysterone  pinoresinol diglucoside  bone strength
基金项目:国家自然科学基金项目(81873318);上海市卫生健康委基金项目(2018JP013);上海市博士点基金项目(B201713);上海中医药大学研究生“创新能力培养”项目(Y2020054);上海中医药大学预算内科研项目(2020LK040);龙华医院龙医学者育苗计划项目(LYTD-71)
作者单位
章喻 张孙正远 王利波 王成龙 蔡珏峰 戴薇薇* 上海中医药大学附属龙华医院科技中心实验室上海 200032 
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中文摘要:
      目的 探讨牛膝成分β-蜕皮甾酮(βEcdysterone,βEcd)联合杜仲成分松脂醇二葡萄糖苷(pinoresinol diglucoside,PDG)治疗糖皮质激素性骨质疏松症的可行性。方法 2月龄SPF级雄性C57BL/6小鼠分为正常对照组、模型组、阿仑膦酸钠(ALN)组、βEcd组、PDG组和βEcd+PDG组。对照组皮下注射100μL生理盐水;模型组与给药组皮下注射地塞米松(2 mg/kg);给药组中,分别皮下注射ALN(0.5 mg/kg)、βEcd(0.5 mg/kg)、PDG(0.5 mg/kg)以及βEcd+PDG(剂量各为0.5 mg/kg)。每周测量体重,计算体质量指数;4周实验结束后以Micro CT、生物力学、ELISA、Western blot方法评估模型及治疗效果。结果 与对照组比较,模型组体质量指数、皮质骨骨矿物质密度(BMD)、股骨弹性模量、弯曲刚度、弯曲强度及最大负重载荷、骨形成标志物P1NP浓度降低(P<0.05),骨吸收标志物β-CTx浓度升高(P<0.05),骨组织细胞凋亡相关蛋白Caspase-3、Bax表达增高(P<0.05);与模型组比较,βEcd-PDG组合提高模型小鼠体质量指数、BMD、股骨弯曲强度和最大负重载荷、P1NP浓度(P<0.05),降低β-CTx浓度(P<0.05),上调抗凋亡因子Bcl-2表达、下调Caspase-3、Bax表达(P<0.05)。结论 βEcd-PDG组合促进GIOP模型小鼠骨形成,增加骨密度、增强骨质量,并可改善骨组织细胞的凋亡水平。
英文摘要:
      Objective To investigate the application of active monomers, β-ecdysterone (βEcd) from Niuxi and pinoresinol diglucoside (PDG) from Duzhong, in the treatment of glucocorticoid-induced osteoporosis (GIOP). Methods Two-month-old C57BL/6 male mice were randomly divided into 6 groups: normal control group, model group (Dex), positive control group, alendronate group (Dex + ALN), βEcd group (Dex + βEcd), PDG group (Dex + PDG), and βEcd combined with PDG group (Dex + βEcd + PDG). Mice in normal control group were subcutaneously injected with the saline. Mice in model group and treatment groups received 2 mg/kg of dexamethasone (Dex). Mice in treatment groups received 0.5 mg/kg of ALN, 0.5 mg/kg of βEcd, 0.5 mg/kg of PDG, or the mixture of 0.5 mg/kg βEcd and 0.5mg/kg PDG with same proportion, respectively. The mice were weighed every week during the experiment, and the body weight index was calculated with the ratio of body weight at the beginning of the study. After 4 weeks, the model and treatment effects were assessed with micro CT, bone biomechanical testing, ELISA, and Western blotting. Results Compared to the control group, treatment with 2 mg/kg of Dex reduced the weight index, BMD of femoral cortical bone, bone quality indicators. and P1NP concentration (P<0.05), and increased β-CTx concentration (P<0.05), while bending strength, maximum bending load and PINP reduced, expression of caspase-3 and Bax protein increased. Compared to the model group, βEcd and PDG improved the weight index, BMD, bending strength, maximum bending load, and PINP, reduced β-CTx, up-regulated Bcl-2 protein expression, and down-regulated the expression of caspase-3 and Bax (P<0.05). Conclusion βEcd combined with PDG ameliorates GC-induced effects in mice by promoting bone formation and enhancing bone strength.
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