基于Notch1信号通路调控巨噬细胞极化改善佐剂关节炎大鼠关节炎症的机制
The mechanism of regulating macrophage polarization based on Notch1 signaling pathway to improve joint inflammation in adjuvant arthritis rats
摘要
Abstract
Objective:To study the impact of the Notch1/Jagged1/RBP-Jκ/Hes1 signaling pathway on macrophage polar-ization and its role in modulating the inflammatory response in rats with adjuvant arthritis(AA).Methods:The rats were random-ly divided into three groups(6 rats):the healthy group(NC),the model group(MC),and the Notch1 inhibitor group(FLI).Medication was administered after 12 days of inducing inflammation.After 30 days,the arthritis index and degree of swelling in the right hind foot joint were measured in each group.The expression levels of CD80+ and CD163+ cells in peripheral blood macro-phages of rats were analyzed by flow cytometry.The levels of IL-4,IL-10,IL-1β,and TNF-α in rat serum were measured by enzyme-linked immunosorbent assay.The expression of Notch1,Jagged1,RBP-Jκ,and Hes1 proteins in rat synovial tissue was detected using Western blot.Results:The degree of swelling and arthritis index in the MC group rats with AA were significantly higher than those in the NC group(P<0.01).CD80+ cell expression was significantly higher compared to the control group(P<0.01),while CD163+ cell expression was significantly lower than the control group(P<0.01).IL-1β and TNF-α expression lev-els were significantly elevated(P<0.01),whereas IL-4 and IL-10 expression levels were significantly decreased(P<0.01).Notch1,RBP-Jκ,Jagged1,and Hes1 protein expression levels were significantly increased(P<0.01).In comparison to the MC group,the rats in the Notch1 inhibitor group exhibited a significant reduction in toe swelling and arthritis index(P<0.01).CD80+ cell expression was significantly decreased(P<0.01),while CD163+ cell expression was significantly increased(P<0.01).IL-1β and TNF-α expression levels were significantly decreased(P<0.05),whereas IL-4 and IL-10 levels were significantly increased(P<0.01).Notch1,Jagged1,Hes1,and RBP-Jκ protein expression levels were significantly decreased(P<0.05).Correlation analysis revealed a positive association between CD80+ and Notch1,Jagged1,Hes1,and RBP-Jκ(P<0.01),while CD163+ showed a negative correlation with the expression of these proteins(P<0.01).Conclusion:The Notch1/Jagged1/RBP-Jκ/Hes1 signaling axis regulates macrophage polarization to M2 type and reduces inflammation in AA rats.关键词
佐剂关节炎/Notch1/Jagged1/RBP-Jκ/Hes1信号轴/巨噬细胞极化Key words
Adjuvant arthritis/Notch1/Jagged1/RBP-Jκ/Hes1 axis/Macrophage polarization分类
医药卫生引用本文复制引用
程静,万磊,赵磊,李舒,李方泽,胡赛赛,陈莹莹..基于Notch1信号通路调控巨噬细胞极化改善佐剂关节炎大鼠关节炎症的机制[J].海南医学院学报,2023,29(23):1780-1785,6.基金项目
This study was supported by National Natural Science Foundation General Project(81973655,82274501) （81973655,82274501）
The Seventh Batch of National Elderly Traditional Chinese Medicine Experts'Academic Experience Inheritance Project of the National Administration of Traditional Chinese Medicine(Guo Zhong Yao Ren Jiao Han[2022]No.76). （Guo Zhong Yao Ren Jiao Han[2022]No.76）
Anhui Provincial Excellent Youth Talent Support Program for Universities(Anhui Education Secretary[2022]No.11) （Anhui Education Secretary[2022]No.11）
Key Laboratory of Xin'an Medical Education Department(2020xayx04) （2020xayx04）
Excellent Youth Talent Support Program for Universities(Anhui Education Secretary[2022]No.11) （Anhui Education Secretary[2022]No.11）
Provincial Education and Teaching Reform Research Project of Anhui Province Higher Education Quality Engineering Project(2022jyxm883) 国家自然基金面上项目(81973655,82274501) （2022jyxm883）
国家中医药管理局第七批全国老中医药专家学术经验继承项目[国中医药人教函(2022)76号].安徽省高校优秀青年人才支持计划项目[皖教秘人(2022)11号] （2022）
新安医学教育部重点实验室(2020xayx04) （2020xayx04）
高校优秀青年人才支持计划项目[皖教秘人(2022)11号],安徽省高等学校质量工程项目省级教育教学改革研究项目(2022jyxm883) （2022）
