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| 固本活血壮骨方经Nrf2/ARE轴调节糖皮质激素性骨质疏松症 |
| Constitution-consolidating, blood-activating and bone strengthening prescription alleviates glucocorticoid-induced osteoporosis via Nrf2/ARE axis |
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| DOI：10.3969/j.issn.1006-7108.2025.11.002 |
| 中文关键词: 骨质疏松症 糖皮质激素 固本活血壮骨方 氧化应激 KEAP-1-Nrf2/ARE信号通路 |
| 英文关键词:osteoporosis glucocorticoid constitution-consolidating, blood-activating, and bone-strengthening prescription oxidative stress Nrf2/ARE axis |
| 基金项目:陕西省教育厅重点科研计划项目（23JS006）；秦创原中医药产业创新聚集区项目（L2024-QCY-ZYYJJQ-X26）；陕西省自然科学基础研究计划面上项目（2025JC-YBMS-1015） |
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| 中文摘要: |
| 目的 通过核因子E2相关因子/抗氧化反应元件（nuclear factor erythroid 2-related factor 2/antioxidant response element，Nrf2/ARE）轴研究固本活血壮骨方（constitution-consolidating，blood-activating and bone-strengthening prescription，GB）改善糖皮质激素性骨质疏松症（glucocorticoid-induced osteoporosis，GIOP）的相关机制。方法 将3月龄SD大鼠随机分为正常对照组、模型组、阿仑膦酸钠组及低、中、高剂量GB组。记录大鼠体重变化；通过显微CT分析大鼠股骨骨密度（bone mineral density, BMD）与骨微结构参数；小动物骨骼强度检测仪评价大鼠股骨骨生物力学性能；Elisa与RT-PCR检测大鼠股骨氧化应激与炎症因子表达；Western blot分析Nrf2/ARE通路相关因子蛋白表达与Nrf2的核转位变化。结果 GB改善了GIOP大鼠体重、BMD、骨微结构参数（BS/TV、BV/TV、Tb.N、Tb.Sp与SMI值）、骨结构强度（P＜0.05），降低了股骨MDA含量、KEAP-1蛋白表达及IL-6和TNF-α的mRNA表达（P＜0.05），增加了CAT与SOD含量及Nrf2、NQO1、HO-1蛋白表达（P＜0.05），并促进了Nrf2核转位。结论 GB通过抑制氧化应激与炎症反应对GIOP发挥保护作用，可能与Nrf2/ARE轴有关。 |
| 英文摘要: |
| Objective To explore the related mechanism of constitution-consolidating, blood-activating, and bone-strengthening prescription (GB) in alleviation of glucocorticoid-induced osteoporosis (GIOP) via nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) axis. Methods Three-month-old Sprague Dawley rats were randomly divided into control group, model group, alendronate sodium group, and low, middle, and high dose group of GB. The changes of weight were recorded. Bone mineral density (BMD) and microstructure coefficient of the femur were detected with micro-CT. Bone biomechanical properties of rats were detected with a small animal bone strength tester. Indexes including oxidative stress and inflammatory in the femur were tested with ELISA and RT-PCR, respectively. Protein expressions related to Nrf2/ARE axis and nuclear translocation of Nrf2 were tested using Western blotting. Results GB improved weight, BMD, microstructure coefficients (BS/TV, BV/TV, Tb.N, Tb.Sp, and SMI value) and bone structural strength in GIOP rats (P<0.05). Meanwhile, GB declined MDA content, the protein expressions of KEAP-1, the mRNA expressions of IL-6 and TNF-α (P<0.05). It also enhanced CAT and SOD content and protein expressions of Nrf2, NQO1, and HO-1 (P<0.05), as well as boosted nuclear translocation of Nrf2. Conclusion GB exerts protective effect on GIOP through inhibiting oxidative stress and inflammatory, which may be related to Nrf2/ARE axis. |
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