中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (8): 1822-1827.doi: 10.4103/1673-5374.387978

• 原著:退行性病与再生 • 上一篇    下一篇

中性粒细胞肽 1激活巨噬细胞:加速瓦勒变性后变性轴突的清除

  

  • 出版日期:2024-08-15 发布日期:2024-01-03
  • 基金资助:
    国家自然科学基金(81971177)
    北京大学人民医院研究与发展基金(RDX2021-01)
    北京市自然科学基金(7222198)

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Yuhui Kou1, 2, 3, #, Yusong Yuan4, #, Qicheng Li1, 3, #, Wenyong Xie1, Hailin Xu1, 2, *, Na Han2, 3, 5, *   

  1. 1Department of Trauma and Orthopedics, Peking University People’s Hospital, Beijing, China; 2National Center for Trauma Medicine, Beijing, China; 3Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education, Beijing, China; 4Department of Orthopedics, China-Japan Friendship Hospital, Beijing, China; 5Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People’s Hospital, Beijing, China
  • Online:2024-08-15 Published:2024-01-03
  • Contact: Hailin Xu, MD, xuhailinfa@163.com; Na Han, PhD, hannaqa@163.com or hannaqa@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 32371048 (to YK); the Peking University People’s Hospital Research and Development Funds, No. RDX2021-01 (to YK); and the Natural Science Foundation of Beijing, No. 7222198 (to NH).

摘要:

在以往研究中,该团队已证实单次肌肉注射中性粒细胞肽 1可以促进坐骨神经挤压损伤后的早期功能恢复。然而,NP-1促进周围神经再生的机制尚不清楚。鉴于中性粒细胞肽 1与巨噬细胞的密切关系,实验假设中性粒细胞肽 1可能通过与巨噬细胞密切相关的机制促进周围神经再生。实验在沃勒氏变性过程中,使用 CUBIC 光学清除技术观察了轴突碎片的吞噬作用。使用蛋白质芯片检测了不同极化状态下巨噬细胞炎症因子的表达。结果显示,中性粒细胞肽 1能促进巨噬细胞的增殖、迁移和吞噬。在中性粒细胞肽 1 的干预下,Wallerian 退化过程中轴突碎片的清除率得到提高。研究还发现,中性粒细胞肽 1 可在体内和体外下调炎症因子白细胞介素1α,-6,-12 和 肿瘤坏死因子α水平。因此,中性粒细胞肽 1可激活巨噬细胞并加速 Wallerian 退化,这可能是中性粒细胞肽 1 加速周围神经再生的机制之一。

https://orcid.org/0000-0003-1829-3852 (Hailin Xu); https://orcid.org/0000-0003-4590-3361 (Na Han)

Abstract: Macrophages play an important role in peripheral nerve regeneration, but the specific mechanism of regeneration is still unclear. Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration. However, the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear. This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury. The functions of RAW 264.7 cells were elucidated by Cell Counting Kit-8 assay, flow cytometry, migration assays, phagocytosis assays, immunohistochemistry and enzyme-linked immunosorbent assay. Axonal debris phagocytosis was observed using the CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) optical clearing technique during Wallerian degeneration. Macrophage inflammatory factor expression in different polarization states was detected using a protein chip. The results showed that neutrophil peptide 1 promoted the proliferation, migration and phagocytosis of macrophages, and CD206 expression on the surface of macrophages, indicating M2 polarization. The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention. Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α, -6, -12, and tumor necrosis factor-α in vivo and in vitro. Thus, the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration, which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Key words: axonal debris, inflammatory factors, macrophages, neutrophil peptide 1, peripheral nerve injury, peripheral nerve regeneration, RAW 264.7 cells, sciatic nerve, Wallerian degeneration