滑膜液中PI3K/AKT/mTOR信号轴介导巨噬细胞极化对膝骨关节炎促炎反应的作用  

PI3K/AKT/mTOR in synovial fluid extends the proinflammatory response of macrophage polarization in knee osteoarthritis

作　　者：蒋总 郭腾逊 姚晓玲 兰维娅 唐芳 马武开 刘佳 Jiang Zong;Guo Tengxun;Yao Xiaoling;Lan Weiya;Tang Fang;Ma Wukai;Liu Jia(Second Clinical Medical College,Guizhou University of Traditional Chinese Medicine,Guiyang 550002;Dept of Rheumatology and Immunology,The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550003)

机构地区：[1]贵州中医药大学第二临床医学院,贵阳550002 [2]贵州中医药大学第二附属医院风湿免疫科,贵阳550003

出　　处：《安徽医科大学学报》2024年第3期377-383,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82160917);贵州省科技计划项目(编号:黔科合平台人才[2020]2202号、黔科合基础-ZK[2023]一般436);贵州省普通高等学校青年科技人才成长项目(编号:黔教合KY字[2022]262号);贵州省卫健委科技基金项目(编号:gzwkj2021-142);贵州中医药大学研究生教育创新计划自然科学项目(编号:YCXZRB202201)。

摘　　要：目的已知PI3K/AKT/mTOR信号通路与膝骨关节炎(KOA)的进展有关,本研究旨在探讨PI3K/AKT/mTOR信号轴介导的巨噬细胞极化诱导是否是KOA进展的原因。方法收集KOA KL-Ⅱ与KL-Ⅲ级患者与正常人的滑膜液,检测滑膜液中M1巨噬细胞(CD80、CD86)与M2巨噬细胞(CD163、CD206)百分比(M1/M2比值),评估巨噬细胞极化细胞因子白细胞介素(IL)-1、IL-6、IL-10、肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β在KOA滑膜液中的表达,并对KOA滑膜液中PI3K/AKT/mTOR信号轴关键分子PI3K、AKT3、mTORC1和诱导性一氧化氮合酶(iONS)进行检测分析。结果与正常人的滑膜液相比,KOA患者中M1型巨噬细胞(CD80、CD86)百分比增加(P<0.01),M1/M2比值升高(P<0.001);KOA组滑膜液中IL-1、IL-6、TNF-α表达也高于对照组(P<0.01),KOA组IL-10、TGF-β表达明显减少(P<0.01);KOA组滑膜液中PI3K/AKT/mTOR信号通路中关键蛋白PI3K、AKT3、mTORC1及下游炎症因子(iONS)高于对照组(P<0.01)。结论在KOA滑膜液中,M1型巨噬细胞极化占据主要地位,M1巨噬细胞极化介导的炎症反应可能是滑膜炎产生的原因,同时PI3K/AKT/mTOR信号通路可能介导M1型巨噬细胞极化参与KOA炎症反应。Objective Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA),this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression.Methods The synovial fluid of KOA KL-Ⅱand KL-Ⅲpatients and normal individuals was collected,and the percentage of M1 macrophages(CD80,CD86)and M2 macrophages(CD163,CD206)in the synovial fluid(M1/M2 ratio)was measured to evaluate the polarization of macrophage cytokines such as IL-1,IL-6,IL-10,and tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-βExpression in KOA synovial fluid,and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K,AKT3,mTORC1,and inducible nitric oxide synthase(iONS)in KOA synovial fluid.Results Compared with the synovial fluid of normal individuals,the percentage of M1 macrophages(CD80,CD86)in KOA patients increased(P<0.01),and the M1/M2 ratio increased(P<0.001);The expression of IL-1,IL-6,and TNF-αin the synovial fluid of the KOA group was also higher than that of the control group(P<0.01),while the expression of IL-10 and TGF-βin the KOA group was significantly reduced(P<0.01);The key proteins PI3K,AKT3,mTORC1,and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01).Conclusion In KOA synovial fluid,M1 macrophage polarization plays a dominant role,and the inflammatory response mediated by M1 macrophage polarization may be the cause of synovitis.At the same time,the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammatory response.

关 键 词：膝骨关节炎 巨噬细胞极化 M1/M2 PI3K/AKT/mTOR信号通路 滑膜液 炎症 

分 类 号：R684[医药卫生—骨科学]