中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (17): 4400-4406.doi: 10.12307/2026.111

• 组织构建细胞学实验 cytology experiments in tissue construction • 上一篇    下一篇

壮骨健膝方抑制人滑膜巨噬细胞炎症反应的作用机制

彭斯伟1，2，杨瑞芳3，陈小华3，郑卓铭3，陈  鹏1，2，肖  艳1，2，苏友新2，郭洁梅2   

  1. 福建中医药大学，1骨伤学院，2中医骨伤及运动康复教育部重点实验室，福建省福州市   350122；3福建中医药大学第一临床医学院，福建省福州市   350122 

  • 收稿日期:2025-05-06 接受日期:2025-06-05 出版日期:2026-06-18 发布日期:2025-12-01
  • 通讯作者: 郭洁梅，博士，副教授，福建中医药大学中医骨伤及运动康复教育部重点实验室，福建省福州市 350122
  • 作者简介:彭斯伟，男，1995年生，福建省漳州市人，汉族，在读博士，主要从事痛风及慢性筋骨病的中医药防治及康复研究。
  • 基金资助:
    国家自然科学基金项目(81774347)，项目负责人：苏友新；国家中医药管理局2021年岐黄学者支持项目(国中医药人教函[2022]6号)，项目负责人：苏友新；福建中医药大学苏友新岐黄学者传承工作室建设项目(闽中医[2023]56号)，项目负责人：苏友新

The mechanism by which Zhuanggu Jianxi Decoction inhibits inflammatory response of human synovial macrophages

Peng Siwei1, 2, Yang Ruifang3, Chen Xiaohua3, Zheng Zhuoming3, Chen Peng1, 2, Xiao Yan1, 2, Su Youxin2, Guo Jiemei2   

  1. 1School of Orthopedics and Traumatology, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China; 2Key Laboratory of Traditional Chinese Medicine Orthopedics and Sports Rehabilitation, Ministry of Education, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China; 3The First Clinical Medical College, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China
  • Received:2025-05-06 Accepted:2025-06-05 Online:2026-06-18 Published:2025-12-01
  • Contact: Guo Jiemei, PhD, Associate professor, Key Laboratory of Traditional Chinese Medicine Orthopedics and Sports Rehabilitation, Ministry of Education, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China
  • About author:Peng Siwei, PhD candidate, School of Orthopedics and Traumatology, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China; Key Laboratory of Traditional Chinese Medicine Orthopedics and Sports Rehabilitation, Ministry of Education, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81774347 (to SYX); 2021 Qihuang Scholar Support Project of the National Administration of Traditional Chinese Medicine, No. Guo Zhongyao Renjiao Han [2022]6 (to SYX); Construction Project of Su Youxin Qihuang Scholar Inheritance Studio of Fujian University of Traditional Chinese Medicine, No. Min Zhongyi [2023]56 (to SYX)

PDF

48

摘要：


文题释义：
人滑膜巨噬细胞：是存在于关节滑膜组织中的一类重要免疫细胞，在维持关节稳态及参与炎症性疾病中发挥关键作用。
炎症细胞模型：脂多糖通过触发炎症信号通路，导致炎症因子大量释放，进而诱导细胞损伤，广泛用于模拟炎症反应引起的细胞损伤机制研究。

背景：滑膜巨噬细胞是滑膜组织中的主要组成细胞之一，是引起滑膜炎症的主要细胞类型。作为目前膝骨关节炎相关研究的热点，课题组前期已针对性开展系列研究，从兔滑膜组织及细胞层面上初步验证了壮骨健膝方可通过调控LXRs/NF-κB通路减缓滑膜炎症，以人滑膜巨噬细胞为研究对象，更贴近膝骨关节炎患者的真实状态，以期进一步阐明壮骨健膝方减轻滑膜炎症的机制。
目的：探究壮骨健膝方含药血清对脂多糖诱导的人滑膜巨噬细胞炎症的影响及潜在分子机制。
方法：①取3月龄新西兰大白兔12只制备壮骨健膝方含药血清及空白血清；②采用1.0 μg/mL脂多糖诱导人滑膜巨噬细胞12 h建立炎症损伤模型，随机分为模型组(体积分数10%空白血清)、含药血清组(体积分数10%含药血清)、LXRα阻滞剂组(体积分数10%含药血清+5 μg LXRα阻滞剂)、N-CoR阻滞剂组(体积分数10%含药血清+5 μg N-CoR阻滞剂)、正常组(体积分数10%空白血清)，干预24 h；③Western blot、RT-qPCR检测各组细胞中LXRα、N-CoR、P50、P65的蛋白及mRNA表达，ELISA检测各组细胞上清液中白细胞介素1β、肿瘤坏死因子α水平。
结果与结论：①与正常组相比，模型组LXRα、N-CoR蛋白和mRNA表达均显著降低(P < 0.01)，模型组P50、P65蛋白和mRNA表达及白细胞介素1β、肿瘤坏死因子α水平均显著升高(P < 0.01)；②与模型组相比，含药血清组LXRα、N-CoR蛋白和mRNA表达均显著升高(P < 0.01)，P50、P65蛋白和mRNA表达及白细胞介素1β、肿瘤坏死因子α水平均显著降低(P < 0.01)；LXRα阻滞剂组、N-CoR阻滞剂组P50、P65蛋白和mRNA表达及白细胞介素1β、肿瘤坏死因子α水平均降低(P < 0.01，P < 0.05)；③与含药血清组相比，LXRα阻滞剂组、N-CoR阻滞剂组LXRα、N-CoR蛋白和mRNA表达均显著降低(P < 0.01)，P50、P65蛋白和mRNA表达及白细胞介素1β、肿瘤坏死因子α水平均升高(P < 0.01，P < 0.05)；④结果表明，壮骨健膝方含药血清能通过上调LXRα、N-CoR蛋白及mRNA表达，下调P50、P65蛋白及mRNA表达，抑制LXRs/NF-κB信号通路的传导，减少下游白细胞介素1β、肿瘤坏死因子α炎症相关指标的分泌，从而缓解人滑膜巨噬细胞炎症反应，起到防治膝骨关节炎的作用。

关键词: 膝骨关节炎, 滑膜炎症, 壮骨健膝方, 人滑膜巨噬细胞, LXRs, NF-κB, 信号通路

Abstract: BACKGROUND: Synovial macrophages are one of the main cell types in the synovial tissue and are the primary cell type causing synovial inflammation. As a current research hotspot in knee osteoarthritis inflammation-related studies, our research group has previously conducted a series of targeted studies, preliminarily verifying through rabbit synovial tissue and cell levels that the prescription of Zhuanggu Jianxi Decoction can alleviate synovial inflammation by regulating the liver X receptors (LXRs)/nuclear factor- kappaB (NF-κB) pathway. This study takes human synovial macrophages as the research object, which is closer to the real state of patients with knee osteoarthritis, with the aim of further clarifying the mechanism by which Zhuanggu Jianxi Decoction reduces synovial inflammation.
OBJECTIVE: To explore the effects and potential molecular mechanism of Zhuanggu Jianxi Decoction-containing serum on lipopolysaccharide-induced synovial inflammation in human synovial macrophages.
METHODS: (1) Twelve 3-month-old New Zealand white rabbits were used to prepare the drug-containing serum of Zhuanggu Jianxi Decoction and blank serum. (2) Human synovial macrophages were induced to establish an inflammatory injury model by lipopolysaccharide (1.0 μg/mL). The cells were randomly divided into the model group (10% blank serum), the drug-containing serum group (10% drug-containing serum), the LXRα blocker group (10% drug-containing serum + 5 μg LXRα blocker), the nuclear receptor co-repressor (N-CoR) blocker group (10% drug-containing serum + 5 μg N-CoR blocker), and the normal group (10% blank serum). All the groups were intervened for 24 hours. (3) Western blot and RT-qPCR were used to detect the expression of LXRα, N-CoR, P50, and P65 proteins and mRNAs in each group of cells, and ELISA was used to detect the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant.
RESULTS AND CONCLUSION: (1) Compared with the normal group, the model group showed significantly decreased LXRα and N-CoR protein/mRNA expressions (P < 0.01), while P50/P65 protein/mRNA expressions and the levels of interleukin-1β/tumor necrosis factor-α were significantly elevated (P < 0.01). (2) Compared with the model group, drug-containing serum significantly upregulated LXRα/N-CoR expressions at protein and mRNA levels and downregulated P50/P65 expressions at protein and mRNA levels as well as the levels of interleukin-1β/tumor necrosis factor-α (P < 0.01). Compared with the model group, both blocker groups showed a reduction in P50/P65 expressions at protein and mRNA levels and the levels of interleukin-1β/tumor necrosis factor-α (P < 0.01, P < 0.05). (3) Compared with the drug-containing serum group, both blocker groups exhibited significantly lower the protein and mRNA expressions of LXRα/N-CoR and higher protein and mRNA expressions of P50/P65 and higher levels of interleukin-1β/tumor necrosis factor-α (P < 0.01, P < 0.05). To conclude, Zhuanggu Jianxi Decoction-containing serum alleviates synovial macrophage inflammation and then prevent/treat knee osteoarthritis by upregulating the expression of LXRα/N-CoR protein and mRNA, downregulating the expression of P50/P65 proteins and mRNA, inhibiting the transmission of the LXRs/NF-κB signaling pathway, and reducing the secretion of downstream inflammatory markers (interleukin-1β and tumor necrosis factor-α).

Key words: knee osteoarthritis, synovial inflammation, Zhuanggu Jianxi Decoction, human synovial macrophages, LXRs, NF-κB, signaling pathway

中图分类号: