[1]吴刚,付富瑞,狄嘉杰,等.施氏滋肾通痹汤调控Wnt/β-catenin信号通路治疗膝骨关节炎的作用机制[J].中国中医骨伤科杂志,2026,34(03):23-29.[doi:10.20085/j.cnki.issn1005-0205.260304]
　WU Gang,FU Furui,DI Jiajie,et al.Mechanism of Shishi Zishen Tongbi Decoction in the Treatment of Knee Osteoarthritis through the Wnt/β-Catenin Signaling Pathway[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2026,34(03):23-29.[doi:10.20085/j.cnki.issn1005-0205.260304]
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施氏滋肾通痹汤调控Wnt/β-catenin信号通路治疗膝骨关节炎的作用机制()

《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第34卷
期数:
2026年03期
页码:
23-29
栏目:
基础研究
出版日期:
2026-03-15

文章信息/Info

Title:
Mechanism of Shishi Zishen Tongbi Decoction in the Treatment of Knee Osteoarthritis through the Wnt/β-Catenin Signaling Pathway
文章编号:
1005-0205(2026)03-0023-07
作者:
吴刚1; 2; 付富瑞3; 4; 狄嘉杰1; 2; 李振宇5; 谌玥燚1; 2; 徐文1; 2; 周于程1; 2; 唐德志3; 4; 徐创龙1; 6; 7△
1宁夏回族自治区中医医院(宁夏回族自治区中医研究院)(银川,750021); 2宁夏医科大学; 3上海中医药大学附属龙华医院; 4上海中医药大学脊柱病研究所; 5陕西中医药大学; 6宁夏医科大学附属自治区中医医院; 7宁夏中西医康复临床医学研究中心
Author(s):
WU Gang1; 2; FU Furui3; 4; DI Jiajie1; 2; LI Zhenyu5; CHEN Yueyi1; 2; XU Wen1; 2; ZHOU Yucheng1; 2; TANG Dezhi3; 4; XU Chuanglong1; 6; 7△
1Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine & TCM Research Institute,Yinchuan 750021,China; 2Ningxia Medical University,Yinchuan 750004,China; 3Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China; 4Institute of Spinal Diseases,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China; 5Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi China; 6Affiliated Hospital of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan 750021,China; 7Ningxia Clinical Medical Research Center for Rehabilitation of Integrative Medicine,Yinchuan 750021,China.
关键词:
施氏滋肾通痹汤;  β-catenin信号通路;  骨关节炎;  分子机制
Keywords:
Shishi Zishen Tongbi decoction;  β-catenin signaling pathway;  osteoarthritis;  molecular mechanism
分类号:
R285.5
DOI:
10.20085/j.cnki.issn1005-0205.260304
文献标志码:
A
摘要:
目的:研究施氏滋肾通痹汤通过调控β-catenin信号通路治疗膝骨关节炎的作用机制。方法:选取30只SD大鼠,随机分为假手术组、模型组和施氏滋肾通痹汤组,每组各10只。采用改良Hulth法建立膝骨关节炎大鼠模型,造模2个月后给予施氏滋肾通痹汤灌胃,于治疗2个月后处死大鼠,取膝关节组织进行指标检测。通过X线与Micro-CT检测评估膝关节骨结构变化; 阿利新蓝-苏木精/橙黄G染色(ABH/OG)及番红O固绿染色观察软骨组织形态; 免疫组化检测β-catenin、Col X、MMP-13、Col Ⅱ等蛋白表达; 采用RT-PCR与Western Blot检测Wnt3a、MMP9、MMP13、Col X、ALP、OC、Axin2等基因及其对应蛋白的表达水平。结果:X线及Micro-CT检测发现,模型组膝关节周围骨赘形成较假手术组明显增多,而施氏滋肾通痹汤组骨赘形成较模型组减少。ABH/OG及番红O固绿染色结果显示,假手术组关节软骨表面光滑,四层结构(表浅层、移行层、放射层及钙化层)清晰,软骨细胞呈柱状排列,无巢聚现象; 模型组表浅层细胞数减少,移行层和放射层可见大量细胞巢聚,潮线前移,出现双潮线; 施氏滋肾通痹汤组软骨组织形态较模型组明显改善。免疫组化结果显示,模型组软骨组织中β-catenin、Col X及MMP-13蛋白表达水平显著高于假手术组(P<0.05),施氏滋肾通痹汤组关节软骨细胞β-catenin、Col X和MMP-13蛋白表达较模型组显著减少(P<0.05)。RT-PCR结果显示,模型组软骨组织中Wnt3a、MMP9、MMP13、Col X、ALP、OC及Axin2等基因表达水平显著高于假手术组(P<0.05),施氏滋肾通痹汤组关节软骨细胞Wnt3a、MMP9、MMP13、Col X、ALP、OC和Axin2基因表达较模型组显著降低(P<0.05)。结论:施氏滋肾通痹汤对膝骨关节炎具有治疗作用,其机制可能与下调β-catenin信号通路相关蛋白及基因表达,从而抑制该通路的异常激活有关。
Abstract:
Objective:To investigate the therapeutic mechanism of Shishi Zishen Tongbi decoction in treating knee osteoarthritis(KOA)through the β-catenin signaling pathway.Methods:Thirty male SPF-grade Sprague-Dawley rats were randomly divided into three groups:the sham-operated group,the model group,and the Shishi Zishen Tongbi decoction group(n=10 each).A modified Hulth method was used to establish KOA models.After two months of modeling,the Shishi Zishen Tongbi decoction group received intragastric administration of the decoction for an additional two months.Upon completion,knee joints were collected for evaluation.X-ray and Micro-CT were used to assess structural changes in subchondral bone.Cartilage morphology was observed using ABH/OG and Safranin O/Fast Green staining.Immunohistochemistry was performed to detect the expression of β-catenin,Col X,MMP-13,and Col Ⅱ.RT-PCR and Western Blot were used to measure the mRNA and protein levels of Wnt3a,MMP-9,MMP-13,Col X,alkaline phosphatase(ALP),osteocalcin(OC)and Axin2.Results:X-ray and Micro-CT analyses demonstrated a significant increase in osteophyte formation around the knee joint in the model group compared with the sham-operated group.However,osteophyte formation was markedly reduced in the Shishi Zishen Tongbi decoction group compared to the model group.Histological evaluations using ABH/OG and Safranin O/Fast Green staining showed a smooth articular cartilage surface and clearly defined four-layer structures(superficial,transitional,radial,and calcified zones)in the sham-operated group,with chondrocytes arranged in regular columnar patterns and no evidence of chondrocyte clustering.In contrast,the model group exhibited reduced cell numbers in the superficial zone,prominent chondrocyte clustering in the transitional and radial zones,forward displacement of the tidemark,and double tidemark formation.The cartilage morphology in the Shishi Zishen Tongbi decoction group was significantly improved relative to that in the model group.Immunohistochemical analysis revealed significantly elevated expression levels of β-catenin,Col X,and MMP-13 in the cartilage tissue of the model group compared to the sham-operated group(P<0.05),while these protein levels were significantly reduced in the Shishi Zishen Tongbi decoction group compared to the model group(P<0.05).Real-time PCR results further confirmed that the expression levels of Wnt3a,MMP9,MMP13,Col X,ALP,OC and Axin2 genes were significantly higher in the model group than in the sham-operated group(P<0.05),whereas these gene expression levels were significantly downregulated in the Shishi Zishen Tongbi decoction group compared to the model group(P<0.05).Conclusion:Shishi Zishen Tongbi decoction exerts therapeutic effects on KOA by modulating the β-catenin signaling pathway,likely through downregulation of key genes and proteins involved in its activation,thus slowing disease progression.

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(收稿日期:2025-07-02)

备注/Memo

备注/Memo:
基金项目:宁夏回族自治区自然科学基金项目(2022AAC02070)
△通信作者 E-mail:mqxcl@163.com
更新日期/Last Update: 2026-03-15