Melatonin improves functional recovery in female rats after acute spinal cord injury by modulating polarization of spinal microglial/macrophages
Melatonin improves functional recovery in female rats after acute spinal cord injury by modulating polarization of spinal microglial/macrophages
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褪黑素通过调节脊髓小胶质细胞/巨噬细胞的极化改善急性脊髓损伤后雌性大鼠的功能恢复
DOI：
10.1002/jnr.24409
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发表时间：
2019-07
影响因子：
4.2
通讯作者：
Chen Xueming
中科院分区：
文献类型：
--
作者：
Zhang Yan;Liu Zongjian;Zhang Wenxiu;Wu Qichao;Zhang Yanjun;Liu Yadong;Guan Yun;Chen Xueming
脊髓损伤（SCI）是一种毁灭性的神经系统疾病，但很少有药物被证明是有效的治疗。神经炎症加重了创伤后的继发性损伤。新出现的证据表明，褪黑激素可能有助于保护神经组织免受SCI后的继发性损伤，但其潜在的机制仍然难以捉摸。小胶质细胞/巨噬细胞极化在调节免疫应答中起重要作用。为了检查褪黑激素是否通过调节脊髓中的小胶质细胞/巨噬细胞极化在急性SCI后发挥神经保护作用，我们在SCI后立即在雌性大鼠中腹膜内注射褪黑激素（50 mg/kg），然后连续7天每天注射（n = 6）。与溶剂给药组（n = 6）相比，褪黑激素给药组的Basso、Beattie和Bresnahan运动评分更高，脊髓腔更小，受损脊髓节段中的裂解半胱天冬酶3免疫荧光染色更少。真实的实时PCR数据显示，与溶剂处理组相比，褪黑激素处理的SCI大鼠脊髓中M1小胶质细胞表型标志物的表达水平降低，M2标志物的表达水平升高。褪黑激素增加了雌性SCI大鼠脊髓组织中CD 206+和Arg 1+细胞的数量，减少了CD 16+和iNOS+细胞的数量，并降低了促炎细胞因子（TNF-α、IL-6和IL-1β）的水平。目前的研究结果表明，褪黑激素可以抑制促炎反应，并促进脊髓中的小胶质细胞/巨噬细胞在SCI早期的M2极化，促进功能恢复。因此，褪黑激素可能代表急性SCI的有希望的治疗候选者。
Spinal cord injury (SCI) is a devastating neurological disorder, but few drugs have proven to be effective for its treatment. Neuroinflammation exaggerates the secondary injury subsequent to trauma. Emerging evidence suggests that melatonin may help protect neural tissue against secondary injury after SCI, but the underlying mechanisms remain elusive. Microglial/macrophages polarization plays an important role in regulating immune responses. To examine whether melatonin exerts neuroprotective effects after acute SCI by regulating microglial/macrophages polarization in the spinal cord, we administered intraperitoneal injections of melatonin (50 mg/kg) in female rats immediately after SCI and then daily for seven consecutive days (n = 6). Compared with the vehicle‐treated group (n = 6), the melatonin‐treated group exhibited a greater Basso, Beattie, and Bresnahan locomotor rating score, smaller spinal cavity, and less cleaved caspase 3 immunofluorescence staining in the injured spinal segments. Real‐time PCR data revealed decreases in the expression levels of M1 microglia phenotypic markers and increases in M2 markers in the spinal cord of melatonin‐treated SCI rats, as compared to levels in the vehicle‐treated group. Melatonin increased the number of CD206+ and Arg1+ cells, decreased the number of CD16+ and iNOS+ cells and reduced the levels of pro‐inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β) in the spinal cord tissue of female SCI rats. Current findings suggest that melatonin may inhibit pro‐inflammatory responses and promote M2 polarization of microglial/macrophages in the spinal cord in the early stage of SCI, facilitating functional recovery. Accordingly, melatonin may represent a promising therapeutic candidate for acute SCI.
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发表时间：
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影响因子：
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