Article(id=1304140196858065069, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304140186485543391, articleNumber=null, orderNo=null, doi=10.7501/j.issn.0253-2670.2026.03.017, pmid=null, cstr=null, oa=null, hot=0, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1762444800000, receivedDateStr=2025-11-07, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1788860852684, onlineDateStr=2026-09-08, pubDate=null, pubDateStr=null, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1788860852684, onlineIssueDateStr=2026-09-08, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1788860852684, creator=13701087609, updateTime=1788860852684, updator=13701087609, issue=Issue{id=1304140186485543391, tenantId=1146029695717560320, journalId=1302319053441957962, year='2026', volume='57', issue='3', pageStart='789', pageEnd='1208', issueExtLink='null', onlineDate='null', pubDate='1770825600000', pubDateStr='2026-02-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1788860850211, creator='13701087609', updateTime=1788860942564, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1304140573955351430, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304140186485543391, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1304140573955351431, tenantId=1146029695717560320, journalId=1302319053441957962, issueId=1304140186485543391, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=990, endPage=1000, ext={EN=ArticleExt(id=1304140197206192303, articleId=1304140196858065069, tenantId=1146029695717560320, journalId=1302319053441957962, language=EN, title=Mechanism of Wutou Decoction in treatment of knee osteoarthritis based on Ihh-Gli signaling pathway, columnId=null, journalTitle=Chinese Traditional and Herbal Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=Objective To explore the mechanism of Wutou Decoction (乌头汤) in treating knee osteoarthritis (KOA) by regulating Indian hedgehog factor (Ihh)-glioma associated oncogene homolog (Gli) signaling pathway. Methods Male SD rats were randomly divided into sham group, model group, celecoxib (24 mg/kg) group, Wutou Decoction low-, medium-, and high-dose (1.05, 2.10, 4.20 g/kg) groups, with 10 rats in each group. The improved anterior cruciate ligament resection technique was used to establish a KOA model, after eight weeks of drug intervention, mechanical pain threshold, thermal pain threshold and climbing ability were measured. ELISA was used to detect the levels of matrix metalloproteinase-3 (MMP-3), MMP-13 and type II collagen (Col II) in serum. The morphological changes of knee joint were observed by hematoxylin-eosin (HE) staining. Micro computed tomography (Micro-CT) technology was used to analyze the changes in bone microstructure of knee joint. Western blotting was used to detect the expressions of Ihh, patched 1 (Ptch1), Gli and MMP-13 proteins in knee joint. Results Compared with sham group, rats in model group showed defects and thinning of cartilage surface layer, decreased and disordered cell arrangement, decreased cross-sectional and coronal bone trabeculae, sparse distribution, decreased bone density, thermal pain threshold and mechanical pain threshold were significantly reduced (P < 0.001), slope angle was decreased (P < 0.001), levels of MMP-3 and MMP-13 in serum were significantly increased (P < 0.05, 0.01), Col II level was significantly decreased (P < 0.05), and expression levels of Ihh-Gli signaling pathway related proteins in knee joint were significantly increased (P < 0.001). Compared with model group, the cartilage surface of rats in Wutou Decoction group was smooth, the number of cells was increased, and the morphology was intact. The knee joint cross-section and coronal bone trabeculae were increased, and the distribution was dense. The thermal pain threshold and mechanical pain threshold were significantly increased (P < 0.05, 0.001), slope angle was increased (P < 0.01, 0.001), levels of MMP-3 and MMP-13 in serum were significantly reduced (P < 0.05), level of Col II was significantly increased (P < 0.05), and expression levels of Ihh-Gli signaling pathway related proteins in knee joint were significantly reduced (P < 0.05, 0.001). Conclusion Wutou Decoction protects articular cartilage by inhibiting excessive activation of Ihh-Gli signaling pathway, reducing abnormal proliferation and differentiation of chondrocytes., authors=YU Yueyue, CHENG Hangjie, MENG Zihan, ZHANG Xu, ZHAO Heli, ZHANG Wenjing, LI Ji'an, ZHANG Yixin, authorsList=YU Yueyue, CHENG Hangjie, MENG Zihan, ZHANG Xu, ZHAO Heli, ZHANG Wenjing, LI Ji'an, ZHANG Yixin, authorCompany=null, correspAuthors=null, 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=1304140197130694830, articleId=1304140196858065069, tenantId=1146029695717560320, journalId=1302319053441957962, language=CN, title=基于Ihh-Gli信号通路探究乌头汤治疗膝骨关节炎的作用机制, columnId=1304140191707456168, journalTitle=中草药, columnName=药理与临床, runingTitle=null, highlight=null, articleAbstract=目的 探讨乌头汤通过调控印度刺猬因子（Indian hedgehog，Ihh）-胶质瘤相关癌基因同源物（glioma-associated oncogene homolog，Gli）信号通路治疗膝骨关节炎（knee osteoarthritis，KOA）的作用机制。方法SD雄性大鼠随机分为假手术组、模型组、塞来昔布（24 mg/kg）组和乌头汤低、中、高剂量（1.05、2.10、4.20 g/kg）组，每组10只。采用改良前交叉韧带切除技术建立KOA模型，给予药物干预8周后，测定机械痛阈值、热痛阈值及爬坡能力；ELISA检测血清中基质金属蛋白酶-3（matrix metalloproteinase-3，MMP-3）、MMP-13和II型胶原蛋白（type Ⅱ collagen，Col Ⅱ）水平；采用苏木素-伊红（hematoxylin-eosin，HE）染色观察膝关节的形态学变化；采用显微计算机断层扫描技术（micro-computed tomography，Micro-CT）分析膝关节的骨微结构变化；采用Western blotting检测膝关节Ihh、斑驳蛋白1（patched 1，Ptch1）、Gli和MMP-13蛋白表达。结果 与假手术组比较，模型组大鼠软骨表层缺损、变薄，细胞减少且排列紊乱，膝关节横截面和冠状面骨小梁减小，分布稀疏，骨密度降低，热痛阈值和机械痛阈值显著降低（P ＜0.001），斜坡角度变小（P ＜0.001），血清中MMP-3、MMP-13水平显著升高（P ＜0.05、0.01），Col Ⅱ水平显著降低（P ＜0.05），膝关节Ihh-Gli信号通路相关蛋白表达水平显著升高（P ＜0.001）。与模型组比较，乌头汤组大鼠软骨表面平整，细胞数量增多且形态完整，膝关节横截面和冠状面骨小梁增多，分布密集，热痛阈值和机械痛阈值显著升高（P ＜0.05、0.001），斜坡角度变大（P ＜0.01、0.001），血清中MMP-3、MMP-13水平显著降低（P ＜0.05），Col Ⅱ水平显著升高（P ＜0.05），膝关节Ihh-Gli信号通路相关蛋白表达水平显著降低（P ＜0.05、0.001）。结论 乌头汤通过抑制Ihh-Gli信号通路过度激活，减少软骨细胞异常增殖与分化，从而保护关节软骨。, authors=虞跃跃1,2 , 成杭洁2 , 孟梓涵2 , 张旭2 , 赵合立2 , 张文静3 , 李继安2,4 , 张一昕1 , authorsList=虞跃跃, 成杭洁, 孟梓涵, 张旭, 赵合立, 张文静, 李继安, 张一昕, authorCompany=1 河北中医药大学, 河北 石家庄 050200; Nat Rev Rheumatol , 2015, 11(9): 552-560.et al . IHH-GLI-1-HIF-2α signalling influences hypertrophic chondrocytes to exacerbate osteoarthritis progression [J]. J Orthop Translat , 2024, 49: 207-217.et al . Hedgehog signalling does not stimulate cartilage catabolism and is inhibited by Interleukin-1β [J]. Arthritis Res Ther , 2015, 17: 373.et al . Gene expression analyses of subchondral bone in early experimental osteoarthritis by microarray [J]. PLoS One , 2012, 7(2): e32356.et al . Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models [J]. Bone Joint Res , 2018, 7(3): 244-251.et al . Evidence that meniscus damage may be a component of osteoarthritis: The Framingham study [J]. Osteoarthritis Cartilage , 2016, 24(2): 270-273.et al . miR-199a-5p reduces chondrocyte hypertrophy and attenuates osteoarthritis progression via the Indian hedgehog signal pathway [J]. J Clin Med , 2023, 12(4): 1313.et al . Hedgehog signalling modulates immune response and protects against experimental autoimmune encephalomyelitis [J]. Int J Mol Sci , 2022, 23(6): 3171.et al . Hedgehog signaling and truncated GLI1 in cancer [J]. Cells , 2020, 9(9): 2114.Growth Factors , 2018, 36(5/6): 187-195.et al . Ihh and Runx2/Runx3 signaling interact to coordinate early chondrogenesis: A mouse model [J]. PLoS One , 2013, 8(2): e55296.
中草药
|药理与临床
2026
, 57
(3) :
990
-1000
基于Ihh-Gli信号通路探究乌头汤治疗膝骨关节炎的作用机制
全屏
虞跃跃1,2 , 成杭洁2 , 孟梓涵2 , 张旭2 , 赵合立2 , 张文静3 , 李继安2,4 , 张一昕1
作者信息
1 河北中医药大学, 河北 石家庄 050200;
通讯作者:
李继安
作者简介:
虞跃跃: 虞跃跃，博士研究生，研究方向为中医药临床应用及其机制研究。E-mail:tcmyuyueyue@ncst.edu.cn
Mechanism of Wutou Decoction in treatment of knee osteoarthritis based on Ihh-Gli signaling pathway
YU Yueyue, CHENG Hangjie, MENG Zihan, ZHANG Xu, ZHAO Heli, ZHANG Wenjing, LI Ji'an, ZHANG Yixin
Affiliations
doi: 10.7501/j.issn.0253-2670.2026.03.017
文章导航
目的 探讨乌头汤通过调控印度刺猬因子（Indian hedgehog，Ihh）-胶质瘤相关癌基因同源物（glioma-associated oncogene homolog，Gli）信号通路治疗膝骨关节炎（knee osteoarthritis，KOA）的作用机制。方法SD雄性大鼠随机分为假手术组、模型组、塞来昔布（24 mg/kg）组和乌头汤低、中、高剂量（1.05、2.10、4.20 g/kg）组，每组10只。采用改良前交叉韧带切除技术建立KOA模型，给予药物干预8周后，测定机械痛阈值、热痛阈值及爬坡能力；ELISA检测血清中基质金属蛋白酶-3（matrix metalloproteinase-3，MMP-3）、MMP-13和II型胶原蛋白（type Ⅱ collagen，Col Ⅱ）水平；采用苏木素-伊红（hematoxylin-eosin，HE）染色观察膝关节的形态学变化；采用显微计算机断层扫描技术（micro-computed tomography，Micro-CT）分析膝关节的骨微结构变化；采用Western blotting检测膝关节Ihh、斑驳蛋白1（patched 1，Ptch1）、Gli和MMP-13蛋白表达。结果 与假手术组比较，模型组大鼠软骨表层缺损、变薄，细胞减少且排列紊乱，膝关节横截面和冠状面骨小梁减小，分布稀疏，骨密度降低，热痛阈值和机械痛阈值显著降低（P ＜0.001），斜坡角度变小（P ＜0.001），血清中MMP-3、MMP-13水平显著升高（P ＜0.05、0.01），Col Ⅱ水平显著降低（P ＜0.05），膝关节Ihh-Gli信号通路相关蛋白表达水平显著升高（P ＜0.001）。与模型组比较，乌头汤组大鼠软骨表面平整，细胞数量增多且形态完整，膝关节横截面和冠状面骨小梁增多，分布密集，热痛阈值和机械痛阈值显著升高（P ＜0.05、0.001），斜坡角度变大（P ＜0.01、0.001），血清中MMP-3、MMP-13水平显著降低（P ＜0.05），Col Ⅱ水平显著升高（P ＜0.05），膝关节Ihh-Gli信号通路相关蛋白表达水平显著降低（P ＜0.05、0.001）。结论 乌头汤通过抑制Ihh-Gli信号通路过度激活，减少软骨细胞异常增殖与分化，从而保护关节软骨。
膝骨关节炎
/
乌头汤
/
Ihh-Gli信号通路
/
关节软骨
/
乌头碱
/
次乌头碱
/
新乌头碱
/
芍药苷
/
甘草苷
/
黄芪甲苷
Objective To explore the mechanism of Wutou Decoction (乌头汤) in treating knee osteoarthritis (KOA) by regulating Indian hedgehog factor (Ihh)-glioma associated oncogene homolog (Gli) signaling pathway. Methods Male SD rats were randomly divided into sham group, model group, celecoxib (24 mg/kg) group, Wutou Decoction low-, medium-, and high-dose (1.05, 2.10, 4.20 g/kg) groups, with 10 rats in each group. The improved anterior cruciate ligament resection technique was used to establish a KOA model, after eight weeks of drug intervention, mechanical pain threshold, thermal pain threshold and climbing ability were measured. ELISA was used to detect the levels of matrix metalloproteinase-3 (MMP-3), MMP-13 and type II collagen (Col II) in serum. The morphological changes of knee joint were observed by hematoxylin-eosin (HE) staining. Micro computed tomography (Micro-CT) technology was used to analyze the changes in bone microstructure of knee joint. Western blotting was used to detect the expressions of Ihh, patched 1 (Ptch1), Gli and MMP-13 proteins in knee joint. Results Compared with sham group, rats in model group showed defects and thinning of cartilage surface layer, decreased and disordered cell arrangement, decreased cross-sectional and coronal bone trabeculae, sparse distribution, decreased bone density, thermal pain threshold and mechanical pain threshold were significantly reduced (P < 0.001), slope angle was decreased (P < 0.001), levels of MMP-3 and MMP-13 in serum were significantly increased (P < 0.05, 0.01), Col II level was significantly decreased (P < 0.05), and expression levels of Ihh-Gli signaling pathway related proteins in knee joint were significantly increased (P < 0.001). Compared with model group, the cartilage surface of rats in Wutou Decoction group was smooth, the number of cells was increased, and the morphology was intact. The knee joint cross-section and coronal bone trabeculae were increased, and the distribution was dense. The thermal pain threshold and mechanical pain threshold were significantly increased (P < 0.05, 0.001), slope angle was increased (P < 0.01, 0.001), levels of MMP-3 and MMP-13 in serum were significantly reduced (P < 0.05), level of Col II was significantly increased (P < 0.05), and expression levels of Ihh-Gli signaling pathway related proteins in knee joint were significantly reduced (P < 0.05, 0.001). Conclusion Wutou Decoction protects articular cartilage by inhibiting excessive activation of Ihh-Gli signaling pathway, reducing abnormal proliferation and differentiation of chondrocytes.
knee osteoarthritis
/
Wutou Decoction
/
Ihh-Gli signaling pathway
/
joint cartilage
/
aconitine
/
hypaconitine
/
mesaconitine
/
paeoniflorin
/
glycyrrhizin
/
astragaloside IV
虞跃跃, 成杭洁, 孟梓涵, 张旭, 赵合立, 张文静, 李继安, 张一昕.
基于Ihh-Gli信号通路探究乌头汤治疗膝骨关节炎的作用机制.
中草药,
2026
, 57
(3)
: 990
-1000
.
DOI: 10.7501/j.issn.0253-2670.2026.03.017
YU Yueyue, CHENG Hangjie, MENG Zihan, ZHANG Xu, ZHAO Heli, ZHANG Wenjing, LI Ji'an, ZHANG Yixin.
Mechanism of Wutou Decoction in treatment of knee osteoarthritis based on Ihh-Gli signaling pathway[J].
Chinese Traditional and Herbal Drugs ,
2026
, 57
(3)
: 990
-1000
.
DOI: 10.7501/j.issn.0253-2670.2026.03.017
参考文献
引证文献
陈天勤, 王树东, 胡哲, 等. 基于肥胖和经筋理论探讨五禽戏对膝骨性关节炎的作用机制 [J/OL]. 辽宁中医药大学学报, (2025-09-08) [2025-09-09]. https://link. cnki.net/urlid/21.1543.r.20250905.1656.002.2.Nat Rev Rheumatol , 2015, 11(9): 552-560.et al . IHH-GLI-1-HIF-2α signalling influences hypertrophic chondrocytes to exacerbate osteoarthritis progression [J]. J Orthop Translat , 2024, 49: 207-217.et al . Hedgehog signalling does not stimulate cartilage catabolism and is inhibited by Interleukin-1β [J]. Arthritis Res Ther , 2015, 17: 373.et al . Gene expression analyses of subchondral bone in early experimental osteoarthritis by microarray [J]. PLoS One , 2012, 7(2): e32356.et al . Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models [J]. Bone Joint Res , 2018, 7(3): 244-251.et al . Evidence that meniscus damage may be a component of osteoarthritis: The Framingham study [J]. Osteoarthritis Cartilage , 2016, 24(2): 270-273.et al . miR-199a-5p reduces chondrocyte hypertrophy and attenuates osteoarthritis progression via the Indian hedgehog signal pathway [J]. J Clin Med , 2023, 12(4): 1313.et al . Hedgehog signalling modulates immune response and protects against experimental autoimmune encephalomyelitis [J]. Int J Mol Sci , 2022, 23(6): 3171.et al . Hedgehog signaling and truncated GLI1 in cancer [J]. Cells , 2020, 9(9): 2114.Growth Factors , 2018, 36(5/6): 187-195.et al . Ihh and Runx2/Runx3 signaling interact to coordinate early chondrogenesis: A mouse model [J]. PLoS One , 2013, 8(2): e55296.
2026年第57卷第3期
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doi: 10.7501/j.issn.0253-2670.2026.03.017
接收时间：2025-11-07
首发时间：2026-09-08
https://castjournals.cast.org.cn/joweb/zcy/CN/10.7501/j.issn.0253-2670.2026.03.017
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2种不同金属材料的力学参数
科 属数 种数 占总种数比例 属 种数 占总种数比例 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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