Zhang Ning, Zhao Lanqing, Li Jinwei, Li Hongxi, Chen Yu
Department of Rheumatology and Immunology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110000, China.
Department of Sleep Medicine Center, The Shengjing Affiliated Hospital, China Medical University, Shenyang 110000, Liaoning, China.
Biomater Res. 2024 Dec 11;28:0089. doi: 10.34133/bmr.0089. eCollection 2024.
Gout is a disease caused by hyperuricemia, characterized by inflammation reactions triggered by macrophage polarization. Colchicine is a commonly used drug for gout treatment, but its mechanism of action remains unclear. The aim of this study was to investigate the regulatory effect of colchicine on macrophage polarization to enhance the therapeutic effectiveness against gout inflammation. To accomplish this, a mouse model was established, and peripheral blood mononuclear cell samples were collected. Single-cell RNA sequencing was employed to reveal cellular heterogeneity and identify key genes. Molecular docking and experimental validation were performed to confirm the binding between the key genes and colchicine. Lentiviral intervention and biochemical indicator detection were conducted to assess the impact of key genes on gout mice. Additionally, the therapeutic effect of colchicine incorporated into neutrophil membrane-coated nanoparticles was investigated. The study found that macrophage polarization plays a critical role in gout, and AHNAK was identified as the key gene through which colchicine affects macrophage polarization. Lentiviral intervention to decrease AHNAK expression was shown to alleviate joint swelling in gout mice and regulate macrophage polarization. Colchicine encapsulated in R4F peptide-modified neutrophil membrane-coated Pluronic F127 nanoparticle (R4F-NM@F127) nanocarriers inhibited M1 macrophage polarization, induced M2 macrophage polarization, alleviated gout, and minimized toxicity to normal tissues. Colchicine suppressed M1 macrophage polarization and induced M2 macrophage polarization by binding to AHNAK protein, thereby alleviating gout. Colchicine incorporated into R4F-NM@F127 nanocarriers can serve as a targeted therapeutic drug to regulate macrophage polarization, alleviate gout, and reduce toxicity to normal tissues.
痛风是一种由高尿酸血症引起的疾病，其特征是巨噬细胞极化引发的炎症反应。秋水仙碱是治疗痛风的常用药物，但其作用机制尚不清楚。本研究的目的是探讨秋水仙碱对巨噬细胞极化的调节作用，以提高对痛风炎症的治疗效果。为此，建立了小鼠模型，并收集了外周血单核细胞样本。采用单细胞RNA测序揭示细胞异质性并鉴定关键基因。进行分子对接和实验验证以确认关键基因与秋水仙碱之间的结合。进行慢病毒干预和生化指标检测以评估关键基因对痛风小鼠的影响。此外，还研究了载于中性粒细胞膜包被纳米颗粒中的秋水仙碱的治疗效果。研究发现巨噬细胞极化在痛风中起关键作用，AHNAK被确定为秋水仙碱影响巨噬细胞极化的关键基因。慢病毒干预降低AHNAK表达可减轻痛风小鼠的关节肿胀并调节巨噬细胞极化。包裹在R4F肽修饰的中性粒细胞膜包被的普朗尼克F127纳米颗粒（R4F-NM@F127）纳米载体中的秋水仙碱可抑制M1巨噬细胞极化，诱导M2巨噬细胞极化，减轻痛风，并将对正常组织的毒性降至最低。秋水仙碱通过与AHNAK蛋白结合抑制M1巨噬细胞极化并诱导M2巨噬细胞极化，从而减轻痛风。载于R4F-NM@F127纳米载体中的秋水仙碱可作为一种靶向治疗药物来调节巨噬细胞极化，减轻痛风，并降低对正常组织的毒性。
