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| 女贞子-枸杞子协同骨化三醇抑制CYP24A1增强骨保护的研究 |
| Mechanism of ligustrum lucidum-clycium barbarum synergizing with calcitriol to inhibit CYP24A1 and activate klotho expression in enhancing vitamin D-mediated bone protection |
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| DOI：10.3969/j.issn.1006-7108.2026.05.001 |
| 中文关键词: 绝经后骨质疏松症 女贞子-枸杞子药对 骨化三醇 维生素D代谢 CYP24A1 |
| 英文关键词:postmenopausal osteoporosis ligustrum lucidum-clycium barbarum herb pair calcitriol vitamin D metabolism CYP24A1 |
| 基金项目:2023年宁夏自然科学基金项目（2023AAC03694）；2025年度龙华医院科技创新基础研究项目（CX202518）；2023年宁夏自然科学基金项目（2023AAC02076）；国自然重点项目（82530121）;上海中医药大学“杏林百人”-杏林青年(赵东峰)上海市中医药研究院科技发展项目(24YJS09)；上海中医药大学附属龙华医院临床和科研创新项目(KC2022003) |
| 作者 | 单位 | | 梁君豪1,2# 徐创龙3,4,5# 施森杰1,2 崔家睿1,2 吴孟举1,2 狄嘉杰3,4 冯润萌2 雷朦2 宋和铃2 唐春兰3,4 原淳淳1,2 唐德志1,2 赵东峰1,2* 王拥军1,2* | 1 上海中医药大学附属龙华医院,上海 200032
2 上海中医药大学,上海 201203
3 宁夏回族自治区中医医院（中医研究院）,宁夏 银川 750021
4 宁夏医科大学附属自治区中医医院,宁夏 银川 750021
5 贵州中医药大学,贵州 贵阳 550025 |
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| 中文摘要: |
| 目的 基于中医“补肾填精”理论与维生素D代谢调控，探讨女贞子-枸杞子药对联合骨化三醇对绝经后骨质疏松小鼠模型的骨保护作用及机制。方法 采用双侧卵巢切除术（OVX）建立骨质疏松小鼠模型，分为假手术组（Sham）、模型组（OVX）、药对组（LLG）、骨化三醇组（CG）及联合治疗组（LLCG）。各组灌胃干预8周，采用Micro-CT检测骨密度（BMD）及骨微结构，三点弯曲试验评估骨强度，Western Blot和PCR检测维生素D信号通路（CYP24A1、Klotho、VDR）表达。体外通过成骨细胞培养评估药对对细胞活性、矿化及维生素D通路的影响。结果 与Sham组相比，OVX组骨密度降低、骨微结构破坏、骨强度下降（P<0.05）。LLG组显著提高骨密度、改善骨微结构及增强骨强度（P<0.05），抑制CYP24A1表达，上调Klotho和VDR表达（P<0.05）。LLCG组效果更显著（P<0.01）。体外实验显示，药对促进成骨细胞分化与矿化，抑制CYP24A1、激活Klotho，增强维生素D骨保护作用（P<0.05）。结论 女贞子-枸杞子药对通过调控维生素D代谢（抑制CYP24A1，上调Klotho和VDR），改善OVX小鼠骨质疏松，促进成骨细胞活性。联合骨化三醇进一步增强骨保护作用，显示协同效应，为中西医结合治疗绝经后骨质疏松提供依据。 |
| 英文摘要: |
| Objective To investigate the bone-protective effect and mechanism of the ligustrum lucidum-lycium barbarum (LLG) herbal pair combined with calcitriol in a postmenopausal osteoporosis mouse model, based on the traditional Chinese medicine (TCM) theory of tonifying kidney and replenishing essence and vitamin D metabolism regulation. Methods A postmenopausal osteoporosis model was established using bilateral ovariectomy (OVX) in mice. The mice were then divided into sham-operated (Sham), model (OVX), herbal pair (LLG), calcitriol (CG), and combined treatment (LLCG) groups. Mice in each group received intragastric administration for 8 weeks. Bone mineral density (BMD) and microarchitecture were assessed using micro-CT. Bone strength was evaluated with three-point bending tests. Expressions of CYP24A1, Klotho, and VDR in vitamin D signaling pathway were measured using Western blotting and PCR. In vitro, osteoblast cultures were used to assess the herbal pair’s effects on cell activity, mineralization, and vitamin D pathway modulation. Results Compared with the Sham group, the OVX group exhibited reduced BMD, impaired bone microarchitecture, and decreased bone strength (P<0.05). The LLG group significantly increased BMD, improved bone microarchitecture, and enhanced bone strength (P<0.05), while suppressing CYP24A1 expression and upregulating Klotho and VDR expressions (P<0.05). The LLCG group showed more pronounced effects (P<0.01). In vitro experiments confirmed that the herbal pair promoted osteoblast differentiation and mineralization, inhibited CYP24A1, activated Klotho, and enhanced vitamin D-mediated bone protection (P<0.05). Conclusion Ligustrum lucidum-lycium barbarum herbal pair relieves OVX-induced osteoporosis and promotes osteoblast activity by regulating vitamin D metabolism and by suppressing CYP24A1 and upregulating Klotho and VDR. Combined with calcitriol, it exerts a synergistic bone-protective effect, providing a basis for integrated TCM and Western medicine treatment of postmenopausal osteoporosis. |
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