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Article(id=1322923497839797061, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923268038078806, articleNumber=null, orderNo=null, doi=10.13193/j.issn.1673-7717.2025.04.033, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793339140615, onlineDateStr=2026-10-30, pubDate=1744214400000, pubDateStr=2025-04-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793339140615, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793339140615, creator=13701087609, updateTime=1793339140615, updator=13701087609, issue=Issue{id=1322923268038078806, tenantId=1146029695717560320, journalId=1255847919539208197, year='2025', volume='43', issue='4', pageStart='1', pageEnd='258', issueExtLink='null', onlineDate='null', pubDate='1744214400000', pubDateStr='2025-04-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793339085826, creator='13701087609', updateTime=1793340586453, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322929562572686061, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923268038078806, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322929562572686062, tenantId=1146029695717560320, journalId=1255847919539208197, issueId=1322923268038078806, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=201, endPage=205, ext={EN=ArticleExt(id=1322923498087260998, articleId=1322923497839797061, tenantId=1146029695717560320, journalId=1255847919539208197, language=EN, title=Effect of Duhuo Jisheng Decoction（独活寄生汤）on Serum TLR4/NF-κB Signaling Pathway in Elderly Patients with Knee Osteoarthritis, columnId=1256183365644968140, journalTitle=Chinese Archives of Traditional Chinese Medicine, columnName=Platform of Provincial Project, runingTitle=null, highlight=null, articleAbstract=
Objective

To observe the effect of Duhuo Jisheng Decoction（独活寄生汤）on Toll-like receptor 4（TLR4）/nuclear transcription factorκB（NF-κB）signaling pathway in elderly patients with knee osteoarthritis.

Methods

A total of 118 elderly patients with knee osteoarthritis were divided into observation group and control group（59 cases in each）according to random number table method. The control group was treated with Glucosamine Hydrochloride Tablets and the observation group was treated with Duhuo Jisheng Decoction on the basis of the control group，4 weeks for 1 course of treatment，a total of 2 courses of treatment. The clinical efficacy of the two groups was compared，and the TCM syndrome scores，Western Ontario and McMaster University Osteoarthritis Index（WOMAC）scale score and visual analogue scale（VAS）score before and after treatment were compared between the two groups. Serum levels of interleukin-6（IL-6），matrix metalloproteinase-1（MMP-1），osteocalcin（BGP），carboxy-terminal peptideβdegradation product of type I procollagen（β-CTX）and carboxy-terminal peptide（PICP）of type I procollagen，and the protein expressions of TLR4 and NF-κB were observed before and after treatment in the two groups.

Results

After treatment，the total effective rate of the observation group was 96.61%，higher than that（83.05%）of control group，and the difference was statistically significant（P<0.05）. After treatment，the scores of TCM syndrome in both groups were lower than those before treatment，and the score of the observation group was lower than that of the control group（P<0.05）. After treatment，the WOMACscores and VASscores of both groups were lower than those before treatment，and the scores of the observation group were lower than those of the control group（P<0.05）. After treatment，the levels of IL-6，MMP-1，TLR4 and NF-κB protein in two groups were lower than those before treatment，and the levels of the observation group were lower than those of the control group（P<0.05）. After treatment，the levels of serum BGP and PICP of the two groups were higher than those before treatment，and the levels of the observation group were higher than those of the control group，and the serumβ-CTX level of the two groups was lower than that before treatment，and the level of the observation group was lower than that of the control group（P<0.05）.

Conclusion

The application of Duhuo Jisheng Decoction in the elderly patients with knee osteoarthritis is beneficial to improve the clinical efficacy，reduce the pain，fatigue and other symptoms，and enhance the joint function. The mechanism of action may be related to improving bone metabolism indexes，inhibiting inflammatory factors through TLR4/NF-κB signaling pathway and alleviating cartilage damage.

, authors=Ying XUE, Yongxiang TIAN, Fengrui LIU, Yao HAO, authorsList=Ying XUE, Yongxiang TIAN, Fengrui LIU, Yao HAO, authorCompany=null, correspAuthors=Yao HAO, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322923503032345435, articleId=1322923497839797061, tenantId=1146029695717560320, journalId=1255847919539208197, language=CN, title=独活寄生汤对老年膝骨关节炎血清TLR4/NF-κB信号通路的影响, columnId=1256183369033965799, journalTitle=中华中医药学刊, columnName=省级项目平台, runingTitle=null, highlight=null, articleAbstract=
目的

观察独活寄生汤用于老年膝骨关节炎疗效及其对Toll样受体4（TLR4）/核转录因子κB（NF-κB）信号通路的影响。

方法

将118例老年膝骨关节炎患者按照随机数字表法分为观察组和对照组，各59例。对照组患者给予盐酸氨基葡萄糖片治疗，观察组在对照组基础上联合独活寄生汤治疗，4周为1个疗程，共治疗2个疗程。比较两组临床疗效，比较两组治疗前后中医证候积分、西安大略和麦克马斯特大学骨关节炎指数（WOMAC）量表评分及视觉模拟量表（VAS）评分，观察两组治疗前后血清白细胞介素-6（IL-6）、基质金属蛋白酶-1（MMP-1）、骨钙素（BGP）、I型前胶原羧基末端肽β降解产物（β-CTX）、I型前胶原羧基末端肽（PICP）水平及TLR4、NF-κB蛋白表达。

结果

治疗后观察组总有效率96.61%（57/59）高于对照组的83.05%（49/59），差异有统计学意义（P<0.05）；治疗后两组各项中医证候积分较治疗前降低，并且观察组均低于对照组（P<0.05）；治疗后，两组WOMAC评分及VAS评分较治疗前降低，并且观察组低于对照组（P<0.05）；治疗后两组IL-6、MMP-1及TLR4、NF-κB蛋白水平较治疗前降低，并且观察组均低于对照组（P<0.05）；治疗后，两组血清BGP、PICP水平较治疗前升高，并且观察组高于对照组，两组血清β-CTX水平较治疗前降低，并且观察组低于对照组（P<0.05）。

结论

独活寄生汤用于老年膝骨关节炎患者有利于提高临床疗效，减轻疼痛、乏力等症状，并改善关节功能，其作用机制可能与改善骨代谢指标、通过TLR4/NF-κB信号通路抑制炎症因子水平、减轻软骨损伤等因素有关。

, authors=薛英, 田永祥, 刘峰瑞, 郝耀, authorsList=薛英, 田永祥, 刘峰瑞, 郝耀, authorCompany=null, correspAuthors=郝耀, authorNote=

薛英（1971-），男，黑龙江拜泉人，副主任医师，硕士，研究方向：骨关节炎，骨折创伤。

, correspAuthorsNote=
郝耀（1985-），男，山西吕梁人，副主任医师，博士，研究方向：骨关节运动损伤。E-mail：。
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薛英（1971-），男，黑龙江拜泉人，副主任医师，硕士，研究方向：骨关节炎，骨折创伤。

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薛英（1971-），男，黑龙江拜泉人，副主任医师，硕士，研究方向：骨关节炎，骨折创伤。

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pageEnd=403, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=LI Z, ZOU Y, FAN D, journalName=J Musculoskelet Neuronal Interact, refType=null, unstructuredReference=LI Z，ZOU Y，FAN D，et al．The mechanism of medial collateral ligament repair in knee osteoarthritis based on the TLR4/MyD88/NF-κB inflammatory signaling pathway［J］．J Musculoskelet Neuronal Interact，2020，20（3）：398-403., articleTitle=The mechanism of medial collateral ligament repair in knee osteoarthritis based on the TLR4/MyD88/NF-κB inflammatory signaling pathway, refAbstract=null), Reference(id=1322923515464262564, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, doi=null, pmid=null, pmcid=null, year=2022, volume=44, issue=7, pageStart=2369, pageEnd=2374, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=张涛, 马书杰, 叶斌, journalName=中成药, refType=null, unstructuredReference=张涛，马书杰，叶斌，等．基于网络药理学和分子对接研究牛膝-杜仲药对治疗膝骨关节炎的作用机制［J］．中成药，2022，44（7）：2369-2374., articleTitle=基于网络药理学和分子对接研究牛膝-杜仲药对治疗膝骨关节炎的作用机制, refAbstract=null), Reference(id=1322923515539760037, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, doi=null, pmid=null, pmcid=null, year=2022, volume=46, issue=2, pageStart=227, pageEnd=233, url=null, language=null, rfNumber=[27], rfOrder=26, authorNames=罗孟雄, 毕亦飞, 王象鹏, journalName=山东中医药大学学报, refType=null, unstructuredReference=罗孟雄，毕亦飞，王象鹏，等．桑寄生治疗骨性关节炎作用机制的网络药理学研究［J］．山东中医药大学学报，2022，46（2）：227-233., articleTitle=桑寄生治疗骨性关节炎作用机制的网络药理学研究, refAbstract=null), Reference(id=1322923515606868902, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, doi=null, pmid=null, pmcid=null, year=2019, volume=30, issue=9, pageStart=1241, pageEnd=1246, url=null, language=null, rfNumber=[28], rfOrder=27, authorNames=段凯旋, 李跃文, 刘和波, journalName=中国药房, refType=null, unstructuredReference=段凯旋，李跃文，刘和波，等．基于网络药理学的羌活-独活药对抗炎作用机制研究［J］．中国药房，2019，30（9）：1241-1246., 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组别例数性别/［例（%）］年龄/（岁，±s）病程/（年，±s）关节炎分级/［例（%）］病变部位/［例（%）］
男女Ⅰ级Ⅱ级Ⅲ级Ⅳ级左膝右膝
对照组5927（45.76）32（54.24）67.96±7.483.51±1.087（11.86）29（49.15）20（33.90）3（5.08）31（52.54）28（47.46）
观察组5924（40.68）35（59.32）68.12±7.253.64±1.197（11.86）31（52.54）17（28.81）4（6.78）26（44.07）33（55.93）
), ArticleFig(id=1322923510556926846, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=CN, label=表1, caption=

两组老年膝骨关节炎患者一般资料比较

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组别例数性别/［例（%）］年龄/（岁，±s）病程/（年，±s）关节炎分级/［例（%）］病变部位/［例（%）］
男女Ⅰ级Ⅱ级Ⅲ级Ⅳ级左膝右膝
对照组5927（45.76）32（54.24）67.96±7.483.51±1.087（11.86）29（49.15）20（33.90）3（5.08）31（52.54）28（47.46）
观察组5924（40.68）35（59.32）68.12±7.253.64±1.197（11.86）31（52.54）17（28.81）4（6.78）26（44.07）33（55.93）
), ArticleFig(id=1322923510653395839, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数显效有效无效总有效
对照组5925（42.37）24（40.68）10（16.95）49（83.05）
观察组5936（61.02）21（35.59）2（3.39）57（96.61）
), ArticleFig(id=1322923510728893312, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=CN, label=表2, caption=

两组老年膝骨关节炎患者临床疗效比较

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组别例数显效有效无效总有效
对照组5925（42.37）24（40.68）10（16.95）49（83.05）
观察组5936（61.02）21（35.59）2（3.39）57（96.61）
), ArticleFig(id=1322923510825362305, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数关节隐痛腰膝酸软体倦乏力
治疗前治疗后治疗前治疗后治疗前治疗后
对照组594.58±1.061.95±0.71*3.79±0.911.47±0.34*3.51±0.791.33±0.41*
观察组594.72±0.961.46±0.35*Δ3.84±1.121.12±0.28*Δ3.47±0.720.96±0.25*Δ
), ArticleFig(id=1322923510917636994, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=CN, label=表3, caption=

两组老年膝骨关节炎患者治疗前后中医证候积分比较（±s）

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组别例数关节隐痛腰膝酸软体倦乏力
治疗前治疗后治疗前治疗后治疗前治疗后
对照组594.58±1.061.95±0.71*3.79±0.911.47±0.34*3.51±0.791.33±0.41*
观察组594.72±0.961.46±0.35*Δ3.84±1.121.12±0.28*Δ3.47±0.720.96±0.25*Δ
), ArticleFig(id=1322923510993134467, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数WOMACVAS评分
治疗前治疗后治疗前治疗后
对照组5965.84±8.2333.14±6.52*6.95±1.225.42±1.25*
观察组5964.39±7.5221.73±5.29*Δ6.83±1.373.48±1.07*Δ
), ArticleFig(id=1322923511081214852, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=CN, label=表4, caption=

两组老年膝骨关节炎患者治疗前后WOMAC评分及VAS评分比较（±s）

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组别例数WOMACVAS评分
治疗前治疗后治疗前治疗后
对照组5965.84±8.2333.14±6.52*6.95±1.225.42±1.25*
观察组5964.39±7.5221.73±5.29*Δ6.83±1.373.48±1.07*Δ
), ArticleFig(id=1322923511173489541, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数IL-6/（pg/mL）MMP-1/（ng/L）TLR4NF-κB
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
对照组5980.25±10.3352.91±7.36*17.51±2.478.71±1.63*2.42±0.631.77±0.42*1.82±0.551.28±0.41*
观察组5981.39±8.8448.27±6.08*Δ17.36±2.815.58±1.42*Δ2.39±0.711.28±0.46*Δ1.74±0.590.91±0.26*Δ
), ArticleFig(id=1322923511269958534, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=CN, label=表5, caption=

两组老年膝骨关节炎患者治疗前后血清炎症因子及TLR4、NF-κB蛋白水平比较（±s）

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组别例数IL-6/（pg/mL）MMP-1/（ng/L）TLR4NF-κB
治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
对照组5980.25±10.3352.91±7.36*17.51±2.478.71±1.63*2.42±0.631.77±0.42*1.82±0.551.28±0.41*
观察组5981.39±8.8448.27±6.08*Δ17.36±2.815.58±1.42*Δ2.39±0.711.28±0.46*Δ1.74±0.590.91±0.26*Δ
), ArticleFig(id=1322923511358038919, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数BGPβ-CTXPICP
治疗前治疗后治疗前治疗后治疗前治疗后
对照组594.11±0.855.41±0.75*0.64±0.090.39±0.07*109.47±12.46132.94±16.37*
观察组593.92±0.736.58±0.86*Δ0.68±0.120.32±0.06*Δ112.63±14.69155.33±18.79*Δ
), ArticleFig(id=1322923511450313608, tenantId=1146029695717560320, journalId=1255847919539208197, articleId=1322923497839797061, language=CN, label=表6, caption=

两组老年膝骨关节炎患者治疗前后骨代谢指标比较（±s）

, figureFileSmall=null, figureFileBig=null, tableContent=
组别例数BGPβ-CTXPICP
治疗前治疗后治疗前治疗后治疗前治疗后
对照组594.11±0.855.41±0.75*0.64±0.090.39±0.07*109.47±12.46132.94±16.37*
观察组593.92±0.736.58±0.86*Δ0.68±0.120.32±0.06*Δ112.63±14.69155.33±18.79*Δ
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独活寄生汤对老年膝骨关节炎血清TLR4/NF-κB信号通路的影响
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薛英 , 田永祥 , 刘峰瑞 , 郝耀
中华中医药学刊 | 省级项目平台 2025,43(4): 201-205
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中华中医药学刊 |省级项目平台 2025 , 43 (4) : 201 -205
独活寄生汤对老年膝骨关节炎血清TLR4/NF-κB信号通路的影响
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薛英, 田永祥, 刘峰瑞, 郝耀
作者信息
  • 山西医科大学第一医院，山西　太原　030001
通讯作者:
郝耀（1985-），男，山西吕梁人，副主任医师，博士，研究方向：骨关节运动损伤。E-mail：。
作者简介:

薛英（1971-），男，黑龙江拜泉人，副主任医师，硕士，研究方向：骨关节炎，骨折创伤。

Effect of Duhuo Jisheng Decoction（独活寄生汤）on Serum TLR4/NF-κB Signaling Pathway in Elderly Patients with Knee Osteoarthritis
Ying XUE, Yongxiang TIAN, Fengrui LIU, Yao HAO
Affiliations
  • The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
出版时间: 2025-04-10 doi: 10.13193/j.issn.1673-7717.2025.04.033
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摘要
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目的

观察独活寄生汤用于老年膝骨关节炎疗效及其对Toll样受体4（TLR4）/核转录因子κB（NF-κB）信号通路的影响。

方法

将118例老年膝骨关节炎患者按照随机数字表法分为观察组和对照组，各59例。对照组患者给予盐酸氨基葡萄糖片治疗，观察组在对照组基础上联合独活寄生汤治疗，4周为1个疗程，共治疗2个疗程。比较两组临床疗效，比较两组治疗前后中医证候积分、西安大略和麦克马斯特大学骨关节炎指数（WOMAC）量表评分及视觉模拟量表（VAS）评分，观察两组治疗前后血清白细胞介素-6（IL-6）、基质金属蛋白酶-1（MMP-1）、骨钙素（BGP）、I型前胶原羧基末端肽β降解产物（β-CTX）、I型前胶原羧基末端肽（PICP）水平及TLR4、NF-κB蛋白表达。

结果

治疗后观察组总有效率96.61%（57/59）高于对照组的83.05%（49/59），差异有统计学意义（P<0.05）；治疗后两组各项中医证候积分较治疗前降低，并且观察组均低于对照组（P<0.05）；治疗后，两组WOMAC评分及VAS评分较治疗前降低，并且观察组低于对照组（P<0.05）；治疗后两组IL-6、MMP-1及TLR4、NF-κB蛋白水平较治疗前降低，并且观察组均低于对照组（P<0.05）；治疗后，两组血清BGP、PICP水平较治疗前升高，并且观察组高于对照组，两组血清β-CTX水平较治疗前降低，并且观察组低于对照组（P<0.05）。

结论

独活寄生汤用于老年膝骨关节炎患者有利于提高临床疗效，减轻疼痛、乏力等症状，并改善关节功能，其作用机制可能与改善骨代谢指标、通过TLR4/NF-κB信号通路抑制炎症因子水平、减轻软骨损伤等因素有关。

膝骨关节炎  /  独活寄生汤  /  Toll样受体4  /  核转录因子κB  /  炎症因子
Objective

To observe the effect of Duhuo Jisheng Decoction（独活寄生汤）on Toll-like receptor 4（TLR4）/nuclear transcription factorκB（NF-κB）signaling pathway in elderly patients with knee osteoarthritis.

Methods

A total of 118 elderly patients with knee osteoarthritis were divided into observation group and control group（59 cases in each）according to random number table method. The control group was treated with Glucosamine Hydrochloride Tablets and the observation group was treated with Duhuo Jisheng Decoction on the basis of the control group，4 weeks for 1 course of treatment，a total of 2 courses of treatment. The clinical efficacy of the two groups was compared，and the TCM syndrome scores，Western Ontario and McMaster University Osteoarthritis Index（WOMAC）scale score and visual analogue scale（VAS）score before and after treatment were compared between the two groups. Serum levels of interleukin-6（IL-6），matrix metalloproteinase-1（MMP-1），osteocalcin（BGP），carboxy-terminal peptideβdegradation product of type I procollagen（β-CTX）and carboxy-terminal peptide（PICP）of type I procollagen，and the protein expressions of TLR4 and NF-κB were observed before and after treatment in the two groups.

Results

After treatment，the total effective rate of the observation group was 96.61%，higher than that（83.05%）of control group，and the difference was statistically significant（P<0.05）. After treatment，the scores of TCM syndrome in both groups were lower than those before treatment，and the score of the observation group was lower than that of the control group（P<0.05）. After treatment，the WOMACscores and VASscores of both groups were lower than those before treatment，and the scores of the observation group were lower than those of the control group（P<0.05）. After treatment，the levels of IL-6，MMP-1，TLR4 and NF-κB protein in two groups were lower than those before treatment，and the levels of the observation group were lower than those of the control group（P<0.05）. After treatment，the levels of serum BGP and PICP of the two groups were higher than those before treatment，and the levels of the observation group were higher than those of the control group，and the serumβ-CTX level of the two groups was lower than that before treatment，and the level of the observation group was lower than that of the control group（P<0.05）.

Conclusion

The application of Duhuo Jisheng Decoction in the elderly patients with knee osteoarthritis is beneficial to improve the clinical efficacy，reduce the pain，fatigue and other symptoms，and enhance the joint function. The mechanism of action may be related to improving bone metabolism indexes，inhibiting inflammatory factors through TLR4/NF-κB signaling pathway and alleviating cartilage damage.

knee osteoarthritis  /  Duhuo Jisheng Decoction（独活寄生汤）  /  Toll-like receptor 4  /  nuclear transcription factor κB  /  inflammatory factor
薛英, 田永祥, 刘峰瑞, 郝耀. 独活寄生汤对老年膝骨关节炎血清TLR4/NF-κB信号通路的影响. 中华中医药学刊, 2025 , 43 (4) : 201 -205 . DOI: 10.13193/j.issn.1673-7717.2025.04.033
Ying XUE, Yongxiang TIAN, Fengrui LIU, Yao HAO. Effect of Duhuo Jisheng Decoction（独活寄生汤）on Serum TLR4/NF-κB Signaling Pathway in Elderly Patients with Knee Osteoarthritis[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (4) : 201 -205 . DOI: 10.13193/j.issn.1673-7717.2025.04.033
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膝骨关节炎是临床常见的慢性关节病，多发于中老年群体，患者存在关节肿胀、疼痛、僵硬等表现，严重者还会出现膝关节变形[1-2]。有关该病病因的研究显示，炎症、肥胖、年龄等因素可能与其发病有关，其主要病理特点表现为关节软骨受损、肌肉萎软无力等[3-4]。目前西医治疗该病常用软骨保护剂、非甾体抗炎药等，虽有一定效果但仍不理想[5]。膝骨关节炎在中医学中可纳入“骨痹”范畴，且根据临床表现，多数患者符合肝肾阴虚的辨证分型，独活寄生汤即立足于补益肝肾的治疗原则，临床以该药治疗膝骨关节炎已取得较好的疗效[6-7]。本研究旨在观察该药用于治疗肝肾阴虚型膝骨关节炎的价值并观察其对Toll样受体4（TLR4）/核转录因子κB（NF-κB）信号通路的影响，现报道如下。
1　资料
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1.1　一般资料
纳入2020年9月—2022年9月本院收治的118例老年膝骨关节炎患者。118例患者以随机数字表法分为观察组和对照组，各59例。两组患者一般资料见表1，性别、年龄、病程、关节炎分级及病变部位比较差异无统计学意义（P>0.05），有可比性。
1.2　诊断标准
1.2.1　西医诊断标准
符合《骨关节炎诊治指南（2007年版）》[8]中相关标准：①患者近1个月内存在反复膝关节疼痛；②X线片显示，患者于站立、负重位下关节间隙变窄、软骨下骨硬化和（或）囊性变、关节缘有骨赘形成；③对关节液进行至少2次常规检查，呈清亮、黏稠，白细胞计数低于2000个/mL；④患者年龄≥40岁；⑤晨僵≤3 min；⑥活动时有骨摩擦音。符合其中①、②项，或符合其中①、③、⑤、⑥项，或符合其中①、④、⑤、⑥项，即可诊断膝骨关节炎。
1.2.2　中医诊断标准
符合《膝骨关节炎中医诊疗专家共识（2015年版）》[9]中相关标准：主症为关节隐隐作痛；次症为腰膝酸软无力，酸困疼痛，遇劳更甚；舌质红，少苔；脉沉细无力。经诊断符合肝肾亏虚证的辨证分型。
1.3　纳入标准
①符合中西医诊断标准及肝肾亏虚证的辨证分型；②年龄≥60岁；③近半年内未使用过激素、非甾体抗炎药物等；④未接受过关节镜手术等外科治疗；⑤患者及其家属均签署知情同意书。
1.4　排除标准
①合并其他骨关节疾病；②病情发展至晚期，膝关节存在严重畸形；③妊娠期或哺乳期女性；④对本研究使用药物过敏；⑤存在严重肝肾功能损伤。本研究经山西医科大学第一医院伦理委员会批准（201934号）。
2　方法
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2.1　分组治疗
对照组患者口服盐酸氨基葡萄糖片（江苏正大清江制药有限公司，国药准字H20060647，规格750 mg），1片/次，2次/d。观察组在对照组的基础上口服独活寄生汤，该药方包括独活15 g，桑寄生10 g，生地黄10 g，牛膝10 g，川芎10 g，当归10 g，茯苓10 g，秦艽10 g，杜仲10 g，党参10 g，防风10 g，白芍10 g，甘草6 g，肉桂5 g，细辛3 g，加水1000 mL煎煮至400 mL，分早晚两次各200 mL温服。4周为1个疗程，共治疗2个疗程。
2.2　观察指标
2.2.1　疗效观察
依据《中药新药临床研究指导原则》[10]对两组疗效进行评估，显效为膝关节僵硬、疼痛、肿胀等症状基本消失，膝关节功能基本正常，活动基本不受限；有效为膝关节僵硬、疼痛、肿胀等症状明显改善，关节活动范围受限程度有所减轻；无效为僵硬、疼痛、肿胀等症状无明显改善，膝关节活动受限。总有效率＝（显效例数＋有效例数）/总例数×100%。
2.2.2　中医证候积分
依据《膝骨关节炎中医诊疗专家共识（2015年版）》[9]中膝骨关节炎辨证分型中肝肾亏虚证的诊断标准及患者的临床表现，对其主症关节隐痛和次症腰膝酸软、体倦乏力进行评分，依据严重程度无、轻、中、重4个等级分别赋分0、1、2、3分。分别于治疗前和治疗8周后进行评分。
2.2.3　西安大略和麦克马斯特大学骨关节炎指数（WOMAC）量表评分及视觉模拟量表（VAS）评分
WOMAC量表[11]包含关节疼痛（5个项目）、僵硬（2个项目）及关节功能（17个项目）三方面，每项0～4分，总分96分，得分越高表示关节炎病情越严重。以VAS评分[12]评估患者的疼痛情况，总分0～10分，得分越高表示疼痛越强。分别于治疗前和治疗8周后进行评分。
2.2.4　实验室指标
采集患者晨起空腹静脉血4 mL，离心后取血清，采用酶联免疫吸附法检测血清白细胞介素-6（IL-6）、基质金属蛋白酶-1（MMP-1）、骨钙素（BGP）、I型前胶原羧基末端肽β降解产物（β-CTX）、I型前胶原羧基末端肽（PICP）水平，采用免疫印迹法检测血清TLR4、NF-κB蛋白表达。分别于治疗前和治疗8周后进行检测。
2.2.5　安全性评价
记录两组治疗期间不良反应发生情况。
2.3　统计学方法
应用SPSS 22.0统计软件处理数据，计数资料用百分比（%）表示，采用χ2检验，计量资料以表示，两组间比较采用t检验，同组内比较采取配对样本t检验，等级资料采用秩和检验，P<0.05为差异有统计学意义。
3　结果
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3.1　临床疗效比较
见表2。与对照组相比，观察组治疗总有效率较高（P<0.05）。
3.2　治疗前后中医证候积分比较
见表3。治疗前，两组各项中医证候积分比较差异无统计学意义（P>0.05）；治疗后两组各项中医证候积分较治疗前降低，并且观察组均低于对照组（P<0.05）。
3.3　治疗前后WOMAC评分及VAS评分比较
见表4。治疗前，两组WOMAC评分及VAS评分比较差异无统计学意义（P>0.05）；治疗后，两组WOMAC评分及VAS评分较治疗前降低，并且观察组低于对照组（P<0.05）。
3.4　治疗前后血清炎症因子及TLR4、NF-κB蛋白水平比较
见表5。治疗前，两组血清IL-6、MMP-1及TLR4、NFκB蛋白水平比较差异无统计学意义（P>0.05）；治疗后两组IL-6、MMP-1及TLR4、NF-κB蛋白水平较治疗前降低，并且观察组均低于对照组（P<0.05）。
3.5　治疗前后骨代谢指标比较
见表6。治疗前，两组血清BGP、β-CTX、PICP比较差异无统计学意义（P>0.05）；治疗后，两组血清BGP、PICP水平较治疗前升高，并且观察组高于对照组，两组血清β-CTX水平较治疗前降低，并且观察组低于对照组（P<0.05）。
3.6　不良反应
治疗期间，两组均未见明显不适及肝肾功能损害等情况。
4　讨论
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膝骨关节炎在中医学领域中属于“骨痹”范畴，并认为“病在骨，骨重不可举，骨髓酸痛寒气至，名曰骨痹”[13]。该病的病因主要与肝肾亏虚有关，其多发于中老年群体，随着年龄增长，精气逐渐衰败，肝藏血主筋，肾藏精、主骨生髓，若肝肾亏虚，则筋骨关节失于濡养，致胫软膝酸，加之负重劳损、风寒湿邪侵袭，引起体内气滞血阻，经脉不通，不通则痛，表现为屈伸受限、关节疼痛等症状[14-15]。目前已有研究认为，该病为本虚标实之证，治疗可用固肾补虚之法，用药宜甘温[16]。
本研究发现，观察组治疗总有效率较高，另外治疗后两组中医证候积分各项均有降低且观察组低于对照组，提示独活寄生汤用于老年膝骨关节炎有利于提高临床疗效，缓解临床症状。此方中独活、桑寄生、肉桂、防风、细辛、秦艽为温辛之品，能解风寒湿邪，可止腰膝背痛；牛膝、杜仲、白芍均有滋阴养血之功效，能够滋补肝肾之阴；甘草、党参、茯苓为补气之品，能够滋补诸脏之阳。其中杜仲、桑寄生、牛膝均有补肝肾、强健筋骨之功效，常为治肾虚腰膝酸痛、筋骨无力之药，诸药合用，共起活血祛瘀、补益肝肾、止痛健骨之功效[17-18]。
本研究发现，治疗后两组血清炎症因子及TLR4、NF-κB蛋白水平均有所改善并且观察组改善幅度较大，提示独活寄生汤用于老年膝骨关节炎有利于减轻机体炎症反应，其作用机制可能与独活寄生汤抑制了TLR4/NF-κB信号通路的激活有关。NF-κB信号通路在人体内广泛存在，NF-κB由IκB家族蛋白和NF-κB家族蛋白共同组成，调控机体内发生的各种免疫反应和炎症反应[19]。NF-κB蛋白二聚体一般情况下与IκB蛋白共同构成三聚体，通常以非活性形式存在于细胞质中，此情况下NF-κB无基因转录功能[20-21]。但机体受到病毒感染、细菌感染和炎症细胞因子等因素刺激时，存在于NFκB信号通路中的IκB蛋白泛素化或磷酸化，引起IκB蛋白加速降解，NF-κB活化后进入细胞核，在特异性DNA位点结合，进而发挥基因转录功能、引导相关蛋白表达[22-23]。NF-κB信号通路对于软骨细胞的增殖和分化具有调节作用，软骨细胞受到炎症因子刺激后，促进IκB激酶合成，引起IκB水解，释放NF-κB，从而导致软骨损伤加剧[24-25]。药理学研究显示[26]，牛膝-杜仲药治疗膝骨关节炎的靶点蛋白涉及多种信号通路，包括TLR4信号通路、NF-κB信号通路、肿瘤坏死因子（TNF）信号通路等，并与炎症反应、软骨细胞凋亡和分化等密切相关。罗孟雄等[27]通过网络药理学相关理论研究桑寄生治疗骨性关节炎的作用机制，该研究发现，与桑寄生相关的信号通路有多条，其中就包含TLR4/NF-κB信号通路等常见通路。
本研究显示，治疗后两组WOMAC评分及VAS评分均有所降低，且观察组低于对照组，提示独活寄生汤用于老年膝骨关节炎有利于减轻疼痛，改善关节功能。现代药理学研究显示[28]，独活中的活性成分香豆素镇痛效果确切，其机制可能是通过调节炎性细胞因子、环氧合酶等改善神经源性和炎性痛觉过敏。廖禹程[29]等研究通过网络药理分析发现独活中的β-谷固醇、蛇床子素等化合物可能是独活发挥镇痛效果的主要活性成分。本研究还发现，治疗后两组血清BGP、β-CTX、PICP水平均有所改善并且观察组改善幅度较大，提示独活寄生汤用于老年膝骨关节炎有利于改善患者的骨代谢状况。可能与独活寄生汤中部分中药材的药理作用有关，牛膝治疗膝骨关节炎的活性成分包括黄连碱、巴马汀、山柰酚、菠甾醇等，其中黄连碱能够促进软骨细胞增殖，促进转化生长因子β1（TGF-β1）mRNA表达提高，从而发挥治疗效果[30]。另外，两组治疗期间均未见明显不良反应和肝肾功能损害，提示独活寄生汤安全性较高。
综上，在常规西药基础上联合独活寄生汤治疗老年膝骨性关节炎有利于提高临床疗效，改善关节功能，减轻临床症状及疼痛，且安全性较好，具有推广价值。可能是通过调控TLR4/NF-κB信号通路抑制炎性反应，减轻软骨损伤。
基金
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  • 山西省科技厅科研基金项目(201901D211481)
  • 山西省留学人员科技活动择优项目(20200037)
文献
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2025年第43卷第4期
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doi: 10.13193/j.issn.1673-7717.2025.04.033
  • 首发时间：2026-10-30
  • 出版时间：2025-04-10
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山西省科技厅科研基金项目(201901D211481)
山西省留学人员科技活动择优项目(20200037)
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    山西医科大学第一医院，山西　太原　030001

通讯作者:

郝耀（1985-），男，山西吕梁人，副主任医师，博士，研究方向：骨关节运动损伤。E-mail：。
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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