姜黄素通过抑制mTOR通路减轻关节炎模型大鼠免疫失衡及骨破坏

doi:10.16352/j.issn.1001-6325.2026.11.1491

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (11): 1491-1500.doi: 10.16352/j.issn.1001-6325.2026.11.1491

姜黄素通过抑制mTOR通路减轻关节炎模型大鼠免疫失衡及骨破坏

余佳雯¹, 汤育琦¹, 陈武², 徐丽萍³, 张艳³, 戴巧定^3*

浙江中医药大学 1.第一临床医学院;2.基础医学院,浙江杭州 310053;
3.浙江省中医药大学附属第一医院(浙江省中医院) 风湿免疫科,浙江杭州 310006

收稿日期:2025-08-12 修回日期:2025-12-30 出版日期:2026-11-05 发布日期:2026-10-26
通讯作者: ^*20043007@zcmu.edu.cn
基金资助:
浙江省医药卫生科技计划(2021KY836);浙江省卫生健康委员会一般项目(2024KY1227)

Curcumin ameliorates immune dysregulation and bone destruction in rat models with collagen-induced arthritis via inhibiting the mTOR signaling pathway

YU Jiawen¹, TANG Yuqi¹, CHEN Wu², XU Liping³, ZHANG Yan³, DAI Qiaoding^3*

1. The First Clinical Medical College; 2. School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou 310053;
3. Department of Rheumatology and Immunology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China

Received:2025-08-12 Revised:2025-12-30 Online:2026-11-05 Published:2026-10-26
Contact: ^*20043007@zcmu.edu.cn

摘要/Abstract

摘要： 目的研究姜黄素对胶原诱导的关节炎(CIA)大鼠免疫异常及骨破坏的干预作用。方法建立CIA大鼠模型。造模成功后分为模型组、姜黄素组和雷帕霉素组。另设正常组。评估大鼠治疗前后的一般情况及足爪肿胀程度、ELISA检测血清中细胞因子和基质金属蛋白酶(MMPs)、HE染色观察关节滑膜炎的组织病理变化、流式细胞测量术检测外周血中Treg/Th17比例、TRAP染色观察足关节破骨细胞数目、Western blot检测骨代谢标志物、RANK/RANKL/OPG蛋白以及滑膜组织中mTOR、AKT、p70S6K的表达。结果与正常组相比,模型组大鼠关节滑膜增生、炎性浸润,血清IL-1β、TNF-α、MMP-1、MMP-3水平均显著升高(P＜0.01),Treg/Th17比例降低(P＜0.05),破骨细胞增多,Ⅰ型胶原C端肽(CTX-1)上升、骨钙素(OC)下降(P＜0.001),RANKL/RANK上调、OPG下调,滑膜组织中AKT1、mTOR、p70S6K表达均升高(P＜0.01)。与模型组比较,姜黄素组的CIA大鼠关节炎明显减轻,促炎细胞因子和MMPs水平降低(P＜0.01),Treg/Th17的比例上调(P＜0.01),IL-10水平升高,IL-17水平降低(P＜0.01),破骨细胞数量减少,活性降低,改善RANKL/RANK/OPG系统的紊乱,AKT1、mTOR、p70S6K的表达水平下降(P＜0.05)。结论姜黄素可纠正Treg/Th17失衡、抑制破骨细胞的分化和活性,其作用机制可能与抑制mTOR信号通路有关。

关键词: 姜黄素, mTOR信号通路, 胶原诱导的关节炎(CIA), 免疫异常, 骨破坏

Abstract: Objective To investigate the therapeutic effects of curcumin on immune dys-regulation and bone destruction in collagen-induced arthritis (CIA) rats. Methods A rat model of CIA was established. After successful modeling, the rats were divided into the model group, curcumin group, rapamycin group, and normal group. The general condition and degree of paw swelling in the rats were evaluated before and after treatment. Serum level of cytokines and matrix metalloproteinases(MMPs) was measured by ELISA. Histopathological changes in synovitis were observed by HE staining microscopy. The ratio of Treg to Th17 in peripheral blood was determined by flow cytometry. The number of osteoclasts in the foot joints was shown by using TRAP staining. Bone metabolism markers,RANK/RANKL/ OPG proteins, as well as the expression of mTOR, AKT, and p70S6K in synovial tissue were detected by Western blot analysis. Results Compared with the normal group, the model group exhibited synovial hyperplasia and inflammatory infiltration along with significantly elevated serum level of IL-1β, TNF-α, MMP-1, and MMP-3(P＜0.01). The Treg/Th17 ratio was decreased(P＜0.05), while osteoclast counting was increased(P＜0.01). Serum 1 collagen C-terminal peptide(CTX-1) level was elevated while that of osteocalcin(OC) was reduced(P＜0.001). The RANKL/RANK pathway was up-regulated, whereas OPG expression was down-regulated. Additionally, the expression level of AKT1, mTOR, and p70S6K in synovial tissue was increased(P＜0.01). Compared to model group, curcumin treatment significantly alleviated arthritis in CIA rats, reduced the level of pro-inflammatory cytokines and MMPs(P＜0.01), and up-regulated Treg/Th17 ratio(P＜0.01). IL-10 level was increased, while IL-17 level was decreased(P＜0.01). Osteoclast numbers and activity were reduced, and the imbalance in the RANKL/RANK/OPG system was ameliorated. Furthermore, the expression level of AKT1, mTOR, and p70S6K was down-regulated(P＜0.05). Conclusions Curcumin restores the Treg/Th17 balance and suppresses osteoclast differentiation and activity, the potential mechanism is considered to be the inhibition of the mTOR signaling pathway.

Key words: curcumin, mTOR signaling pathway, collagen-induced arthritis (CIA), immune deregulation, bone destruction

中图分类号:

余佳雯, 汤育琦, 陈武, 徐丽萍, 张艳, 戴巧定. 姜黄素通过抑制mTOR通路减轻关节炎模型大鼠免疫失衡及骨破坏[J]. 基础医学与临床, 2026, 46(11): 1491-1500.

YU Jiawen, TANG Yuqi, CHEN Wu, XU Liping, ZHANG Yan, DAI Qiaoding. Curcumin ameliorates immune dysregulation and bone destruction in rat models with collagen-induced arthritis via inhibiting the mTOR signaling pathway[J]. Basic & Clinical Medicine, 2026, 46(11): 1491-1500.

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姜黄素通过抑制mTOR通路减轻关节炎模型大鼠免疫失衡及骨破坏

Curcumin ameliorates immune dysregulation and bone destruction in rat models with collagen-induced arthritis via inhibiting the mTOR signaling pathway

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