中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (7): 1669-1678.doi: 10.12307/2026.057

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

白藜芦醇在炎症微环境下促进骨髓间充质干细胞的成骨分化

邹玉莲1，2，3，陈朝沛1，2，3，黄海霞1，2，3，兰玉燕1，2，3，刘  敏1，2，3，黄  婷1，2，3   

  1. 1西南医科大学附属口腔医院修复科，四川省泸州市   646000；2口颌面修复重建和再生泸州市重点实验室，四川省泸州市   646000；3 西南医科大学口腔医学研究所，四川省泸州市   646000
  • 收稿日期:2024-12-05 修回日期:2025-05-08 接受日期:2025-05-29 出版日期:2026-03-08 发布日期:2025-08-18
  • 通讯作者: 黄海霞，硕士，副主任医师，西南医科大学附属口腔医院修复科，四川省泸州市 646000；口颌面修复重建和再生泸州市重点实验室， 四川省泸州市 646000；西南医科大学口腔医学研究所，四川省泸州市 646000
  • 作者简介:邹玉莲，女，1999 年生，四川省资阳市人，汉族，西南医科大学在读硕士，主要从事口腔种植、口腔修复的基础与临床研究。
  • 基金资助:
    泸州市重点研发科技计划项目(2024SYF143)，项目负责人：黄海霞

Resveratrol promotes osteogenic differentiation of bone marrow mesenchymal stem cells in an inflammatory microenvironment

Zou Yulian1, 2, 3, Chen Chaopei1, 2, 3, Huang Haixia1, 2, 3, Lan Yuyan1, 2, 3, Liu Min1, 2, 3, Huang Ting1, 2, 3   

  1. 1Department of Prosthodontics, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Luzhou 646000, Sichuan Province, China; 3Institute of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China 
  • Received:2024-12-05 Revised:2025-05-08 Accepted:2025-05-29 Online:2026-03-08 Published:2025-08-18
  • Contact: Huang Haixia, MS, Associate chief physician, Department of Prosthodontics, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Luzhou 646000, Sichuan Province, China; Institute of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • About author:Zou Yulian, Master candidate, Department of Prosthodontics, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Luzhou 646000, Sichuan Province, China; Institute of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    Key Research & Development Science and Technology Plan Project of Luzhou City, No. 2024SYF143 (to HHX)

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摘要：



文题释义：

白藜芦醇：是一种天然的非黄酮类多酚化合物，广泛存在于多种植物中，除具有抗炎、抗氧化、抗衰老和抗肿瘤等作用外，在减少骨质流失、控制和预防骨质疏松症方面也展现了巨大潜力，有望应用于改善种植体周围炎患者口内种植体骨结合。
FoxO1信号通路：是叉头转录因子家族的成员，可调控多种细胞过程，如细胞增殖、分化、凋亡、衰老、氧化还原平衡和炎症等，能通过抗氧化应激效应发挥保护作用。

摘要
背景：国内种植体周围炎的发病率不断攀升，对种植体的修复效果造成极大影响。研究白藜芦醇能否改善炎症微环境下骨髓间充质干细胞的生物学活性及作用机制，对探索种植体周围炎相关治疗药物开发提供一定的理论支撑。
目的：研究白藜芦醇在炎症微环境下对骨髓间充质干细胞成骨分化的影响。
方法：采用全骨髓贴壁法提取、纯化SD大鼠骨髓间充质干细胞，将细胞分为3组：正常对照组、脂多糖组(1 μg/mL)、脂多糖+白藜芦醇(1 μmol/L)组，干预24 h。DCFH-DA活性氧荧光探针检测活性氧水平，RT-qPCR检测促炎基因白细胞介素1β、白细胞介素18、肿瘤坏死因子α mRNA表达，成骨诱导7 d后进行碱性磷酸酶染色，成骨诱导21 d后进行茜素红染色，成骨诱导7 d后RT-qPCR检测成骨基因Runx2、Osx mRNA表达，成骨诱导7 d后Western blot检测FoxO1、NLRP3蛋白表达。
结果与结论：①白藜芦醇减轻炎症微环境对骨髓间充质干细胞碱性磷酸酶活性及钙化结节形成的抑制作用；②白藜芦醇可抑制炎症微环境中骨髓间充质干细胞促炎基因白细胞介素1β、白细胞介素18、肿瘤坏死因子α mRNA表达并上调成骨基因Runx2、Osx mRNA表达；③白藜芦醇可下调炎症微环境中骨髓间充质干细胞的活性氧水平；④白藜芦醇可促进FoxO1蛋白表达并抑制NLRP3蛋白表达；⑤结果表明，白藜芦醇(1 μmol/L)通过激活FoxO1信号通路、抑制NLRP3炎症小体表达，从而减少炎症因子的释放、清除过量活性氧，最终促进炎症微环境下骨髓间充质干细胞的成骨分化。


https://orcid.org/0009-0003-4774-2255 (邹玉莲) 


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: 骨髓间充质干细胞, 白藜芦醇, 脂多糖, 种植体周围炎, 成骨分化, FoxO1, 活性氧, NLRP3

Abstract: BACKGROUND: The incidence of peri-implantitis is increasing in China, which greatly affects restorative results of implants. To explore whether resveratrol can improve the biological activity and mechanism of bone marrow mesenchymal stem cells in inflammatory microenvironment can provide some theoretical support for the development of therapeutic drugs related to peri-implantitis.
OBJECTIVE: To investigate the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells in an inflammatory microenvironment.
METHODS: Bone marrow mesenchymal stem cells were extracted and purified from SD rats by whole bone marrow apposition method. Bone marrow mesenchymal stem cells were divided into three groups as follows: normal control group, lipopolysaccharide group (1 μg/mL), lipopolysaccharide + resveratrol (1 μmol/L) group, and received the intervention for 24 hours. DCFH-DA reactive oxygen species fluorescent probe was used to detect reactive oxygen species levels. RT-qPCR was used to detect the mRNA expression of pro-inflammatory genes interleukin-1β, interleukin-18, and tumor necrosis factor-α. Alkaline phosphatase staining was performed 7 days after osteogenic induction. Alizarin red staining was performed 21 days after osteogenic induction. RT-qPCR was used to detect the mRNA expression of osteogenic genes Runx2 and Osx 7 days after osteogenic induction. Western blot assay was used to detect the protein expression of FoxO1 and NLRP3 7 days after osteogenic induction. 
RESULTS AND CONCLUSION: (1) Resveratrol alleviated the inhibitory effect of the inflammatory microenvironment on alkaline phosphatase activity and calcified nodule formation in bone marrow mesenchymal stem cells. (2) Resveratrol inhibited mRNA expression of pro-inflammatory genes interleukin-1β, interleukin-18, and tumor necrosis factor-α and up-regulated mRNA expression of osteogenic genes Runx2 and Osx in bone marrow mesenchymal stem cells in the inflammatory microenvironment. (3) Resveratrol downregulated reactive oxygen species levels in bone marrow mesenchymal stem cells in the inflammatory microenvironment. (4) Resveratrol promoted FoxO1 protein expression and inhibited NLRP3 protein expression. (5) The results confirm that resveratrol (1 μmol/L) activates the FoxO1 signaling pathway and inhibits the expression of NLRP3 inflammatory vesicles, which reduces the release of inflammatory factors, removes excessive reactive oxygen species, and ultimately promotes the osteogenic differentiation of bone marrow mesenchymal stem cells in the inflammatory microenvironment.  


Key words: bone marrow mesenchymal stem cell, resveratrol, lipopolysaccharide, peri-implantitis, osteogenic differentiation, FoxO1, reactive oxygen species, NLRP3

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