丁基苯酞通过促进小胶质细胞/巨噬细胞 M2 极化来发挥脊髓损伤的抗炎作用。
Butylphthalide has an Anti-Inflammatory Role in Spinal Cord Injury by Promoting Macrophage/Microglia M2 Polarization via p38 Phosphorylation.
机构信息
Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi Province, China.
Department of Orthopaedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China.
出版信息
Spine (Phila Pa 1976). 2020 Sep 1;45(17):E1066-E1076. doi: 10.1097/BRS.0000000000003503.
STUDY DESIGN
An experimental animal study of treatment of spinal cord injury (SCI).
OBJECTIVE
This report aims to evaluate the in vivo effects of butylphthalide NBP on SCI biology and to explore its potential mechanism.
SUMMARY OF BACKGROUND DATA
SCI causes great damage to humans. The inflammatory and reconstructive processes after SCI is regulated by activation of astroglial and microglial cells. Activated microglia/macrophages can be divided into M2 (anti-inflammatory) and M1 (pro-inflammatory) phenotypes. Butylphthalide (3-n-butylphthalide or NBP) treatment can significantly alleviate ischemic brain damage, and further study has confirmed that central neuroprotective effects can be realized by converting M1 polarized microglia/macrophages to the M2 phenotype. Thus far, it remains unknown whether NBP can modulate the transition of macrophages/microglia between the M1 and M2 phenotypes.
METHODS
We randomly divided male mice into three groups (sham group, SCI group, SCI+ NBP group). Molecular and histological tests were performed to detect the macrophage/microglia polarization as well as the potential mechanism of NBP in vivo and in vitro.
RESULT
It was found that NBP treatment significantly attenuated the motor dysfunction and neuronal apoptosis induced by SCI. Treatment with NBP could also reduce pro-inflammatory cytokine release after SCI and could facilitate macrophage/microglia M2 polarization and inhibit M1 polarization after SCI. To verify the findings in animal experiments, we examined the effect of NBP on BV2 cell polarization, the results showed that NBP treatment could enhance M2 polarization and inhibit M1 polarization, and that M2 polarization occurred in a p38-dependent manner.
CONCLUSION
NBP plays an important role in the anti-inflammatory response in SCI via the facilitation of macrophage/microglia M2 polarization as well as the inhibition of macrophage/microglia M1 polarization. The M2 polarization of macrophages/microglia occurs via activation of p38 pathway.
LEVEL OF EVIDENCE
研究设计
脊髓损伤（SCI）治疗的实验动物研究。
目的
本报告旨在评估丁基苯酞 NBP 对 SCI 生物学的体内作用，并探讨其潜在机制。
背景资料概要
SCI 会对人体造成巨大伤害。SCI 后，星形胶质细胞和小胶质细胞的激活调节着炎症和重建过程。激活的小胶质细胞/巨噬细胞可分为 M2（抗炎）和 M1（促炎）表型。丁基苯酞（3-正丁基苯酞或 NBP）治疗可显著减轻缺血性脑损伤，进一步研究证实，通过将 M1 极化的小胶质细胞/巨噬细胞转化为 M2 表型，可实现中枢神经保护作用。迄今为止，尚不清楚 NBP 是否可以调节巨噬细胞/小胶质细胞之间的 M1 和 M2 表型转化。
方法
我们将雄性小鼠随机分为三组（假手术组、SCI 组、SCI+NBP 组）。进行分子和组织学测试，以检测体内和体外 NBP 对巨噬细胞/小胶质细胞极化的潜在机制。
结果
发现 NBP 治疗可显著减轻 SCI 引起的运动功能障碍和神经元凋亡。NBP 治疗还可以减少 SCI 后促炎细胞因子的释放，并促进 SCI 后巨噬细胞/小胶质细胞 M2 极化，抑制 M1 极化。为了验证动物实验中的发现，我们检查了 NBP 对 BV2 细胞极化的影响，结果表明 NBP 治疗可以增强 M2 极化并抑制 M1 极化，并且 M2 极化发生在 p38 依赖性方式。
结论
NBP 通过促进巨噬细胞/小胶质细胞 M2 极化和抑制巨噬细胞/小胶质细胞 M1 极化在 SCI 中的抗炎反应中发挥重要作用。巨噬细胞/小胶质细胞的 M2 极化通过激活 p38 途径发生。
证据水平
3 级。
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