[关键词]
[摘要]
目的 基于Ⅰ型胶原合成降解率探讨淫羊藿和女贞子配伍对大鼠骨质疏松模型的影响及可能机制。方法 取Wistar雄性大鼠60只,随机分为6组,即正常对照组、模型对照组、淫羊藿组(9.5 g·kg-1)、女贞子组(9.5 g·kg-1)、淫羊藿女贞子配伍组(淫羊藿∶女贞子=4∶3,9.5 g·kg-1)、雷洛昔芬阳性对照组(6.25 mg·kg-1),每组10只,自由饮水、摄食。除正常对照组外,其余各组大鼠均用0.5 % 羧甲基纤维素钠(CMC-Na)配成的维甲酸混悬液按70 mg·kg-1灌胃,正常对照组大鼠以0.5 % CMC-Na灌胃,连续造模2周。在模型复制的同时,各组动物灌胃给予相应的药物,正常对照组和模型对照组给予等量的生理盐水灌胃,每日1次,共3周。检测骨密度、生物力学、血清骨钙素(BGP)及Ⅰ型前胶原氨基端前肽(PINP)、Ⅰ型前胶原羧基端前肽(PICP)、Ⅰ型胶原交联羧基末端肽(ICTP)水平,并对实验数据进行相关性分析。结果 与正常对照组比较,模型对照组大鼠骨密度和生物力学性能显著下降(P< 0.01),BGP含量及PINP、PICP、ICTP水平显著升高(P< 0.05,P< 0.01);与模型对照组比较,淫羊藿女贞子配伍可显著升高骨密度(P< 0.01),增强骨生物力学性能(P< 0.01),下调血清BGP及PINP、PICP、ICTP水平(P< 0.05);相关性分析结果显示骨密度、生物力学性能与反映Ⅰ型胶原合成降解率的各指标间存在显著负相关(P< 0.05,P< 0.01)。结论 Ⅰ型胶原合成降解率的加快与骨质疏松的发生密切相关,淫羊藿女贞子配伍对Ⅰ型胶原代谢水平的调节作用可能是其防治骨质疏松症的机制之一。
[Key word]
[Abstract]
Objective To investigate the therapeutic effect and its possible mechanisms of Herba Epimedii and Fructus Ligustri Lucidi for osteoporosis based on typeⅠcollagen metabolism. Methods Sixty male Wistar rats were randomly divided into six different groups according to the body mass:normal control group,model group,Herba Epimedii group(9.5 g·kg-1),Fructus Ligustri Lucidi group(9.5 g·kg-1),combination group of(Herba Epimedii and Fructus Ligustri Lucidi at the combination proportion of 4∶3,9.5 g·kg-1),and positive drug group(raloxifene at the dose of 6.25 mg·kg-1). All rats tool drinking water and food intake freely. Rats except those in the normal control group received intramuscular injection of 70 mg·kg-1 of retinoic acid for two weeks to establish osteoporosis model,and the medication groups were treated with intragastric administration of corresponding medicine once a day for three weeks during the modeling. Outcomes of bone density,biomechanical indicators,bone gla protein(BGP),carboxyterminal crosslinked propeptide of typeⅠprocollagen(PICP),aminoterminal propeptide of typeⅠ procollagen(PINP),and crosslinked carboxy-terminal peptide of typeⅠcollagen(ICTP) were detected. Results Bone density and biomechanical properties were significantly lower(P< 0.01),while the serum contents of BGP,PINP,PICP and ICTP were significantly higher in the model group than those in the normal control group(P< 0.05 or P< 0.01). Compared with the model group,the combination of Herba Epimedii and Fructus Ligustri Lucidi could significantly increase bone density and biomechanical properties(P< 0.01),while down-regulate serum BGP,PINP,PICP and ICTP levels significantly(P< 0.05). The results of correlation analysis showed that bone density and biomechanical properties were negatively correlated with each indicator that reflected the synthesis and degradation rate of typeⅠcollagen(P< 0.05 or P< 0.01). Conclusion Acceleration of synthesis and degradation of typeⅠcollagen is closely related with the development of osteoporosis. The regulation of the combination of Herba Epimedii and Fructus Ligustri Lucidi on typeⅠcollagen metabolism may be one of its preventive and therapeutic mechanisms for osteoporosis.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金资助项目(81373814);北京市教育委员会科技计划面上项目(KM201310025012);北京中医药薪火传承“3+3”工程二室一站建设项目(2012-SZ-C-42)。