基于RANKL/OPG通路探讨补肾壮骨方联合机械振动对去卵巢大鼠骨代谢的调控机制OA
Regulatory mechanism of Bushen Zhuanggu Formula combined with mechanical vibration on bone metabolism in ovariectomized rats via the RANKL/OPG pathway
目的 探究补肾壮骨方联合机械振动对去卵巢大鼠骨代谢的影响及其分子机制.方法 48只SD雌性大鼠随机分为假手术组、模型组、补肾壮骨方组、机械振动组和联合治疗组,采用卵巢切除术建立骨质疏松模型.通过正交实验优化振动参数(频率30 Hz、振幅2 mm、每日2次、每次15 min)与给药方案(10 g/kg,给药后4 h进行振动训练).8周干预后,采用DEXA法检测骨密度,ELISA法测定血清RANKL、OPG水平,Micro-CT分析骨微结构,qPCR检测Wnt/β-catenin、MAPK/ERK等信号通路相关基因表达.结果 联合治疗组股骨骨密度较模型组提高34.6％(P＜0.05),显著优于单一治疗组;血清RANKL水平降低42.3％,OPG水平升高38.6％,RANKL/OPG比值明显下调;骨小梁数量增加52.7％,骨微结构显著改善.膜受体表达分析显示β1-integrin、Piezo1、ERα等受体mRNA表达协同上调,信号通路检测证实Wnt/β-catenin通路活性提高162.9％,MAPK/ERK通路激活增加109.5％.结论 补肾壮骨方联合机械振动通过协同上调膜受体转录、激活多条骨代谢信号通路及优化RANKL/OPG平衡,产生显著协同增效作用,为绝经后骨质疏松的中西医结合治疗提供了实验依据.
Objective To investigate the effects of Bushen Zhuanggu Formula combined with mechanical vibra-tion on bone metabolism in ovariectomized(OVX)rats and to elucidate the underlying molecular mechanisms,with a fo-cus on the RANKL/OPG signaling pathway.Methods Forty-eight female Sprague-Dawley rats were randomly as-signed to five groups:sham-operated group,OVX model group,Bushen Zhuanggu Formula group,mechanical vibration group,and combination therapy group.An osteoporosis model was established by bilateral ovariectomy.Vibration parame-ters were optimized using an orthogonal experimental design(frequency 30 Hz,amplitude 2 mm,twice daily for 15 min per session),and the herbal formula was administered orally at a dose of 10 g/kg,followed by vibration training 4 hours post-administration.After 8 weeks of intervention,bone mineral density(BMD)was measured by dual-energy X-ray absorptiometry(DEXA).Serum levels of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)were quantified by ELISA.Bone microarchitecture was evaluated using micro-computed tomography(micro-CT).Quantitative real-time PCR(qPCR)was performed to assess the expression of genes related to the Wnt/β-cate-nin and MAPK/ERK signaling pathways.Results Compared with the OVX model group,femoral BMD in the combina-tion therapy group increased by 34.6％(P＜0.05),which was significantly greater than that observed in either monother-apy group.Serum RANKL levels were reduced by 42.3％,while OPG levels increased by 38.6％,resulting in a marked-ly decreased RANKL/OPG ratio.Micro-CT analysis revealed a 52.7％increase in trabecular number and substantial im-provement in bone microarchitecture.Membrane receptor analysis demonstrated synergistic upregulation of β1-integrin,Piezo1,and estrogen receptor α(ERα)mRNA expression.Pathway analysis further confirmed significant activation of the Wnt/β-catenin pathway(increase of 162.9％)and enhanced MAPK/ERK signaling(increase of 109.5％)in the com-bination therapy group.Conclusion Bushen Zhuanggu Formula combined with mechanical vibration exerts synergistic os-teoprotective effects in ovariectomized rats by coordinately upregulating mechanosensitive and hormone-related membrane receptors,activating multiple bone metabolic signaling pathways,and restoring RANKL/OPG balance.These findings pro-vide experimental evidence supporting an integrative therapeutic strategy for postmenopausal osteoporosis.
戴杰;杨红;陈艺菲;黄莉;谭新;邓伟民
中国人民解放军南部战区总医院康复医学科(广东 广州 510010)中国人民解放军南部战区总医院康复医学科(广东 广州 510010)广州中医药大学第一临床医学院2024级中医学5+3一体化岱翰国医班(广东 广州 510006)前海人寿广州总医院康复医学科(广东 广州 511300)中国人民解放军南部战区总医院康复医学科(广东 广州 510010)前海人寿广州总医院康复医学科(广东 广州 511300)
医药卫生
补肾壮骨方机械振动骨代谢信号通路骨代谢去卵巢大鼠
Bushen Zhuanggu Formulamechanical vibrationbone metabolism signaling pathwaybone metab-olismovariectomized rats
《广东医学》 2026 (2)
179-185,7
广州市增城区科技计划项目(2021ZCMS08)
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