优韧集胶囊对去势骨质疏松症大鼠的作用及其机制

作者：高云航1，李 晗1，宋 玲1，陈腾飞1，侯红平1，康丽娟2，彭 博1，李 鹏2，叶祖光1，张广平1

单位：1.中国中医科学院中药研究所，北京 100700； 2.河北御芝林生物科技有限公司，河北 石家庄 050000

引用：引用：高云航，李晗，宋玲，陈腾飞，侯红平，康丽娟，彭博，李鹏，叶祖光，张广平.优韧集胶囊对去势骨质疏松症大鼠的作用及其机制[J].中医药导报,2025,31(1):13-19.

DOI：10.13862/j.cn43-1446/r.2025.01.003

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摘要：目的：探讨优韧集胶囊（YRJ）对去势骨质疏松症大鼠的保护作用，并基于骨保护素（OPG）/核因子-κB受体活化因子配体（RANKL）/核因子-κB受体活化因子（RANK）信号通路探究其作用机制。方法：将60只SD雌性大鼠随机分为假手术组、模型组、戊酸雌二醇组（0.1 mg/kg）、优韧集低剂量组（175.0 mg/kg）、优韧集中剂量组（350.0 mg/kg）、优韧集高剂量组（700.0 mg/kg），每组10只。采用手术摘除双侧卵巢的方法复制骨质疏松症模型，随后灌胃给予相应药物，共12周。12周后记录大鼠禁食体质量，采用Micro CT检测大鼠股骨微观结构；酶联免疫吸附试验（ELISA）检测血清钙（Ca）、磷（P）、甲状旁腺激素（PTH）、碱性磷酸酶（ALP）、骨钙素（BGP）及抗酒石酸酸性磷酸酶（TRACP-5b）水平；逆转录聚合酶链式反应（RT-qPCR）检测骨组织OPG mRNA、RANKL mRNA及RANK mRNA表达水平；蛋白免疫印迹（Western blotting）法检测骨组织中OPG、RANKL及RANK蛋白表达水平。结果：模型组大鼠体质量、骨小梁分离度（Tb.Sp）高于假手术组（P<0.05），骨密度（BMD）、骨小梁数（Tb.N）、骨小梁厚度（Tb.Th）、骨体积分数（BV/TV）、骨矿物质含量（BMC）低于假手术组（P<0.05）；优韧集低剂量组、优韧集中剂量组、优韧集高剂量组、戊酸雌二醇组大鼠体质量、Tb.Sp均低于模型组（P<0.05），BMD、Tb.N、Tb.Th、BV/TV及BMC均高于模型组（P<0.05）。模型组大鼠血清Ca、ALP及BGP水平低于假手术组（P<0.05），血清PTH、TRACP-5b水平高于假手术组（P<0.05）；优韧集低剂量组、优韧集中剂量组、优韧集高剂量组、戊酸雌二醇组大鼠血清Ca、BGP水平均高于模型组（P<0.05）；优韧集高剂量组、戊酸雌二醇组大鼠血清PTH水平均低于模型组（P<0.05）；优韧集低剂量组、优韧集高剂量组、戊酸雌二醇组大鼠血清ALP水平均高于模型组（P<0.05）；优韧集中剂量组、戊酸雌二醇组大鼠血清TRACP-5b水平均低于模型组（P<0.05）。模型组大鼠骨组织OPG mRNA相对表达量低于假手术组（P<0.05），RANKL mRNA、RANK mRNA相对表达量高于假手术组（P<0.05）；优韧集中剂量组、优韧集高剂量组、戊酸雌二醇组大鼠骨组织OPG mRNA相对表达量均高于模型组（P<0.05），RANKL mRNA相对表达量低于模型组（P<0.05）；优韧集高剂量组、戊酸雌二醇组大鼠骨组织RANK mRNA相对表达量均低于模型组（P<0.05）。模型组大鼠骨组织OPG蛋白相对表达量低于假手术组（P<0.05），RANKL、RANK蛋白相对表达量高于假手术组（P<0.05）；优韧集中剂量组、优韧集高剂量组、戊酸雌二醇组大鼠骨组织OPG蛋白相对表达量均高于模型组（P<0.05）；优韧集低剂量组、优韧集高剂量组、戊酸雌二醇组大鼠骨组织RANKL蛋白相对表达量均低于模型组（P<0.05）；优韧集高剂量组、戊酸雌二醇组大鼠骨组织RANK蛋白相对表达量均低于模型组（P<0.05）。结论：优韧集胶囊能改善去势大鼠骨质疏松症，具有促进骨形成、抑制骨吸收的作用，其机制可能与调控OPG/RANKL/RANK信号通路相关。

关键词：骨质疏松症；OPG/RANKL/RANK；优韧集胶囊；骨形成；骨吸收；大鼠

Abstract：Objective: To investigate the protective effect of Yurenji capsules (YRJ) on ovariectomy-induced osteoporosis in rats, and to explore the underlying mechanisms based on the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) signaling pathway. Methods: Totally 60 female SD rats were randomly divided into sham group, model group, estradiol valerate group (0.1 mg/kg), low-dose YRJ group (175.0 mg/kg), medium-dose YRJ group (350.0 mg/kg) and high-dose YRJ group (700.0 mg/kg), with 10 rats in each group. An osteoporosis model was established by bilateral ovariectomy, followed by gavage administration of the corresponding drugs for a total of 12 weeks. After 12 weeks, the fasting body weight of the rats was recorded. Micro CT was used to assess the microstructural changes in the femur. Serum levels of calcium (Ca), phosphorus (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), osteocalcin (BGP) and tartrate-resistant acid phosphatase (TRACP-5b) were analyzed using enzyme linked immunosorbent assay (ELISA). The expression levels of OPG mRNA, RANKL mRNA and RANK mRNA in bone tissue were determined using reverse transcription quantitative PCR (RT-qPCR). Western blotting was employed to measure the protein expression levels of OPG, RANKL and RANK in the bone tissue. Results: The model group showed higher body weight and Tb.Sp than sham group (P<0.05), while lower BMD, Tb.N, Tb.Th, BV/TV and BMC than sham group (P<0.05). The low-dose YRJ group, medium-dose YRJ group, high-dose YRJ group and estradiol valerate group showed lower body weight and Tb.Sp than model group (P<0.05), while higher BMD, Tb.N, Tb.Th, BV/TV and BMC than model group (P<0.05). The model group showed lower serum levels of Ca, ALP and BGP than sham group (P<0.05), while higher PTH and TRACP-5b levels than model group (P<0.05). The low-dose YRJ group, medium-dose YRJ group, high-dose YRJ group and estradiol valerate group showed higher serum Ca and BGP levels than model group (P<0.05). The high-dose YRJ group and estradiol valerate group showed lower serum PTH levels than model group (P<0.05); The low-dose YRJ group, high-dose YRJ group and estradiol valerate group showed higher serum ALP levels than model group (P<0.05), and the medium-dose YRJ and estradiol valerate groups showed lower serum TRACP-5b levels than model group (P<0.05). The model group showed lower relative expression of OPG mRNA in bone tissue, than sham group (P<0.05), while higher relative expression of RANKL mRNA and RANK mRNA than sham group (P<0.05). The medium-dose YRJ group, high-dose YRJ group and estradiol valerate group showed higher relative expression of OPG mRNA than model group (P<0.05), while lower relative expression of RANKL mRNA than model group (P<0.05). The high-dose YRJ group and estradiol valerate group showed lower relative expression of RANK mRNA levels than model group (P<0.05). The model group showed lower relative expression of OPG protein in bone tissue, than sham group (P<0.05), and higher relative expression of RANKL and RANK protein levels than sham group (P<0.05). The medium-dose YRJ group, high-dose YRJ group and estradiol valerate group showed higher relative expression of OPG protein levels than model group (P<0.05). The low-dose YRJ group, high-dose YRJ group and estradiol valerate group showed lower RANKL protein levels than model group (P<0.05), and the high-dose YRJ group and estradiol valerate group showed lower RANK protein levels than model group (P<0.05). Conclusion: YRJ are effective in improving osteoporosis in ovariectomized rats by promoting bone formation and inhibiting bone resorption. The underlying mechanisms may be associated with the regulation of the OPG/RANKL/RANK signaling pathway.

Key words：osteoporosis; OPG/RANKL/RANK; Yurenji capsules; bone formation; bone resorption; rat

发布时间：2025-11-28

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