The effect of melatonin (MT) on spinal cord injury (SCI) has attracted increasing research attention. However, the specific role and molecular mechanism of MT on SCI have not been elucidated. An experiment was performed to investigate the effect and molecular mechanism of MT on the neuronal autophagy after SCI and its effect on the recovery of nerve function. The rats were randomly divided into four treatment groups: the SCI+MT+EX527 (SIRT1 inhibitor), SCI+MT, SCI, and sham operation groups. On the 14th day after SCI, MT significantly promoted the recovery of motor function in the hind limbs according to the results of Basso, Beattie, and Bresnahan scores. At the same time, MT treatment resulted in reduced activation of cleaved-caspase-3, cleaved-caspase-9, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neurons and increased the survival of motoneurons in the anterior horn of the spinal cord on the 14th day after SCI, which exerted its neuroprotection. Furthermore, western blot and immunofluorescence double staining were performed to verify the molecular mechanism of effect of MT on SCI, and results showed the significantly upregulated expressions of Beclin-1, light chain-3B, SIRT1, p-AMPK proteins in the spinal cord tissue of MT-treated rats on the 14th day after SCI, however, the effect of MT on autophagy was reversed by EX527 (SIRT1 inhibitor), which implied that MT activated autophagy via SIRT1/AMPK signaling pathway after SCI. Similarly, the neuroprotective effects of MT on SCI were also inhibited after the SIRT1/AMPK signaling pathway was suppressed by EX527. Taken together, these results suggest that MT inhibits the apoptosis and activates autophagy of nerve cells after SCI and ultimately exerts the neuroprotective effect by SIRT1/AMPK signaling pathway.

中文翻译：

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褪黑激素通过SIRT1/AMPK信号通路激活自噬抑制细胞凋亡对脊髓损伤的神经保护作用

褪黑激素 (MT) 对脊髓损伤 (SCI) 的影响已引起越来越多的研究关注。然而，MT对SCI的具体作用和分子机制尚未阐明。通过实验研究MT对SCI后神经元自噬的作用及其分子机制及其对神经功能恢复的影响。将大鼠随机分为四个治疗组：SCI+MT+EX527（SIRT1抑制剂）、SCI+MT、SCI和假手术组。脊髓损伤后第14天，根据Basso、Beattie和Bresnahan评分结果，MT显着促进后肢运动功能恢复。同时，MT 处理导致 cleaved-caspase-3、cleaved-caspase-9、和末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性神经元，增加脊髓前角运动神经元在 SCI 后第 14 天的存活，发挥其神经保护作用。此外，通过蛋白质印迹和免疫荧光双染色验证了MT对SCI影响的分子机制，结果显示脊髓组织中Beclin-1、轻链-3B、SIRT1、p-AMPK蛋白的表达显着上调。在 SCI 后第 14 天 MT 治疗的大鼠中，MT 对自噬的影响被 EX527（SIRT1 抑制剂）逆转，这表明 MT 在 SCI 后通过 SIRT1/AMPK 信号通路激活自噬。同样，在 SIRT1/AMPK 信号通路被 EX527 抑制后，MT 对 SCI 的神经保护作用也受到抑制。