Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Bioengineered. 2022 May;13(5):11794-11809. doi: 10.1080/21655979.2022.2073063.
After spinal cord injury (SCI), a large number of blood-derived macrophages infiltrate the lesion site and phagocytose myelin debris to become foamy macrophages, which leads to chronic inflammation. The drug D-4F, an apolipoprotein A-I peptidomimetic made of D-amino acids, has been reported to promote the lipid metabolism of foamy macrophages in atherosclerosis. However, the role and mechanism of D-4F in SCI are still unclear. In this study, we found that D-4F can promote the removal of myelin debris, reduce the formation of foamy macrophages in the lesion core and promote neuroprotection and recovery of motor function after SCI. These beneficial functions of D-4F may be related to its ability to upregulate the expression of ATP-binding cassette transporter A1 (ABCA1), the main transporter that mediates lipid efflux in foamy macrophages because inhibiting the activity of ABCA1 can reverse the effect of D-4F . In conclusion, D-4F may be a promising candidate for treating SCI by promoting the clearance of myelin debris by foamy macrophages via the ABCA1 pathway.
脊髓损伤（SCI）后，大量血液来源的巨噬细胞浸润损伤部位并吞噬髓磷脂碎片成为泡沫巨噬细胞，导致慢性炎症。药物 D-4F 是一种由 D-氨基酸组成的载脂蛋白 A-I 模拟肽，据报道可促进动脉粥样硬化中泡沫巨噬细胞的脂质代谢。然而，D-4F 在 SCI 中的作用和机制尚不清楚。在这项研究中，我们发现 D-4F 可促进髓磷脂碎片的清除，减少损伤核心中泡沫巨噬细胞的形成，并促进 SCI 后的神经保护和运动功能恢复。D-4F 的这些有益作用可能与其上调三磷酸腺苷结合盒转运体 A1（ABCA1）表达的能力有关，ABCA1 是介导泡沫巨噬细胞中脂质外排的主要转运体，因为抑制 ABCA1 的活性可以逆转 D-4F 的作用。总之，D-4F 可能通过 ABCA1 途径促进泡沫巨噬细胞清除髓磷脂碎片，成为治疗 SCI 的有希望的候选药物。
