中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (6): 1341-1347.doi: 10.12307/2025.995

• 骨组织构建 bone tissue construction •    下一篇

β-石竹烯对小鼠膝骨关节炎的作用及机制

陈  驹1,郑锦畅2,梁  振2,黄成硕1,林  颢2,曾  莉1   

  1. 1澳门科技大学中医药学院,中国澳门特别行政区  999078;2广东医科大学附属医院骨科中心,广东省湛江市  524000

  • 收稿日期:2024-10-30 接受日期:2024-12-31 出版日期:2026-02-28 发布日期:2025-07-12
  • 通讯作者: 曾莉,教授,博士生导师,澳门科技大学中医药学院,中国澳门特别行政区 999078
  • 作者简介:陈驹,男,1990年生,广东省茂名市人,汉族,博士,主要从事中西医药学研究。
  • 基金资助:
    广东省科技计划项目(2023A1414020048),项目参与人:陈驹;广东省医学科学技术研究基金项目(B2024006),项目负责人:梁振;广东省医学科学技术研究基金项目(B2024110),项目负责人:郑锦畅

Effect and mechanism of beta-caryophyllene in mice with osteoarthritis

Chen Ju1, Zheng Jinchang2, Liang Zhen2, Huang Chengshuo1, Lin Hao2, Zeng Li1   

  1. 1Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao Special Administrative Region 999078, China; 2Orthopedic Center, the Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China
  • Received:2024-10-30 Accepted:2024-12-31 Online:2026-02-28 Published:2025-07-12
  • Contact: Zeng Li, Professor, Doctoral supervisor, Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao Special Administrative Region 999078, China
  • About author:Chen Ju, PhD, Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao Special Administrative Region 999078, China
  • Supported by:
    Guangdong Science and Technology Program, No. 2023A1414020048 (to CJ [project participant]); Guangdong Medical Science and Technology Research Fund, Nos. B2024006 (to LZ) and B2024110 (to ZJC) 

摘要:


文题释义:
骨关节炎:是一种常见的关节退行性疾病,多由关节软骨磨损、退变及骨质增生等引发,主要累及膝、髋、脊柱等关节,导致疼痛、肿胀、僵硬与活动受限。骨关节炎发病与年龄、肥胖、创伤等因素密切相关。
β-石竹烯:是源于丁香、肉桂等植物的天然植物油,化学结构独特,属双环倍半萜烯类。β-石竹烯具有抗炎、抗氧化、抗凋亡和减轻神经损伤等多种药理活性,在关节炎、神经及心血管等疾病的防治研究中具有极大的开发价值与潜力。

背景:β-石竹烯具有抗氧化、抗炎及抗凋亡等多种药理活性,可能对骨关节炎具有较好的治疗作用。
目的:探讨β-石竹烯对小鼠膝骨关节炎的作用及机制。
方法:采用随机数字表法将40只C57BL/6J小鼠随机分为假手术组(n=10)、模型组(n=10)、β-石竹烯低剂量组(n=10)和β-石竹烯高剂量组(n=10),后3组采用Hulth法构建膝骨关节炎模型,造模4周后,β-石竹烯低、高剂量组分别给予70,140 mg/(kg·d)β-石竹烯灌胃,假手术组、模型组给予生理盐水灌胃,1次/d,连续给药4周。给药结束后取材,苏木精-伊红染色观察膝关节形态学变化,ELISA法检测血清中炎症因子(肿瘤坏死因子α、白细胞介素1β、白细胞介素6、白细胞介素10)水平,化学发光法检测氧化应激指标(谷胱甘肽过氧化物酶、超氧化物歧化酶、丙二醛),免疫组化和Western Blot检测膝关节音猬因子/胶质瘤相关癌基因同源物1信号通路关键蛋白表达。
结果与结论:①与假手术组比较,模型组小鼠膝关节可见大量炎症细胞浸润,软骨组织损伤严重,血清肿瘤坏死因子α、白细胞介素1β、白细胞介素6、白细胞介素10和丙二醛水平均升高(P < 0.05),谷胱甘肽过氧化物酶、超氧化物歧化酶活性降低(P < 0.05),音猬因子、胶质瘤相关癌基因同源物1蛋白表达升高(P < 0.05);②与模型组比较,β-石竹烯低、高剂量组小鼠膝关节炎症细胞浸润减少,软骨组织损伤明显减轻,血清肿瘤坏死因子α、白细胞介素1β、白细胞介素6、白细胞介素10和丙二醛水平均降低(P < 0.05),谷胱甘肽过氧化物酶、超氧化物歧化酶活性升高(P < 0.05),音猬因子、胶质瘤相关癌基因同源物1蛋白表达降低(P < 0.05),并且以β-石竹烯高剂量组改善更明显;③结果表明,β-石竹烯可能通过音猬因子/胶质瘤相关癌基因同源物1信号通路减轻炎症与氧化应激损伤,进而改善膝骨关节炎。
https://orcid.org/0000-0001-5083-2129(陈驹)

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: β-石竹烯, 骨关节炎, 音猬因子, 胶质瘤相关癌基因同源物1, 信号通路, 小鼠, 工程化组织构建

Abstract: BACKGROUND: β-Caryophyllene has a variety of pharmacological activities such as antioxidant, anti-inflammatory and anti-apoptotic, which may have a better therapeutic effect on osteoarthritis.
OBJECTIVE: To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis. 
METHODS: Forty C57BL/6J mice were randomly divided into sham group, model group, low-dose β-caryophyllene group and high-dose β-caryophyllene group, with 10 mice in each group. Hulth method was used to construct an osteoarthritis model in the latter three groups. Four weeks after modeling, 70 and 
140 mg/kg/d β-caryophyllene was intragastrically given in the low- and high-dose β-caryophyllene groups, respectively, and normal saline was given by gavage in the sham group and the model group, once a day, for 4 weeks. After administration, knee joint morphological changes were observed by hematoxylin-eosin staining, serum levels of inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-10) were detected by ELISA, and oxidative stress indexes (glutathione peroxidase, superoxide dismutase, and malondialdehyde) were detected by chemiluminescence. The expression levels of key proteins in the Sonic hedgehog (Shh)/glioma associated oncogene homolog 1 (Gli1) signaling pathway were detected by immunohistochemistry and western blot. 
RESULTS AND CONCLUSION: (1) Compared with the sham group, a large number of inflammatory cells infiltrated in the knee joint of mice in the model group, cartilage tissue was seriously damaged, serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10 and malondialdehyde were significantly increased (P < 0.01), the activities of glutathione peroxidase and superoxide dismutase were significantly decreased (P < 0.01), and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased (P < 0.01). (2) Compared with the model group, in the low- and high-dose β-caryophyllene groups, inflammatory cell infiltration in the mouse knee joint was decreased, cartilage tissue injury was alleviated, serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and malondialdehyde were significantly decreased (P < 0.05), the activities of glutathione peroxidase and superoxide dismutase were significantly increased (P < 0.01), and the expression levels of Shh and Gli1 in the knee joint were significantly decreased (P < 0.01). The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group. To conclude, β-caryophyllene can improve osteoarthritis, and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway. 

Key words: β-caryophyllene, osteoarthritis, sonic hedgehog, glioma associated oncogene homolog 1, signaling pathway, mouse, engineered tissue construction 

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