MicroRNAs (miRNAs) are implicated in the pathogenesis of spinal cord injury (SCI) as primary regulators. Previous studies have reported that miR-324-5p is involved in the modulation of neural injury, while the underlying mechanisms of miR-324-5p in SCI remain unclear. In a SCI rat model, miR-324-5p was significantly upregulated in the spinal cord tissues after SCI. Downregulation of miR-324-5p via injection of adeno-associated viruses (AAV) expressing miR-324-5p inhibitor relieved animal motor deficits and pathological changes in the tissues. Furthermore, downregulation of miR-324-5p significantly altered the expression of genes regulating neural growth, apoptosis, and the inflammatory and antioxidant response, which are implicated in SCI pathogenesis. In a H₂O₂-induced cell injury model, miR-324-5p silencing rescued the elevated apoptosis of PC12 cells. Finally, miR-324-5p directly targeted the 3’-untranslated region of NAD-dependent protein deacetylase sirtuin-1 (Sirt1) and negatively regulated the levels of Sirt1, an anti-inflammatory protein involved in SCI. Silencing of Sirt1 aggravated SCI and rescued the effects of miR-324-5p downregulation in rats. Overall, our findings indicated that silencing of miR-324-5p alleviates the loss of animal locomotion and concurrently mediates several degenerative processes relevant to the pathogenesis of SCI by Sirt1, which may provide clues for SCI treatment.

MicroRNAs (miRNAs)作为主要调节因子参与脊髓损伤 (SCI) 的发病机制。先前的研究报道，miR-324-5p 参与神经损伤的调节，而 miR-324-5p 在 SCI 中的潜在机制仍不清楚。在 SCI 大鼠模型中，SCI 后脊髓组织中的 miR-324-5p 显着上调。通过注射表达 miR-324-5p 抑制剂的腺相关病毒 (AAV) 下调 miR-324-5p 可缓解动物运动缺陷和组织中的病理变化。此外，miR-324-5p 的下调显着改变了调节神经生长、细胞凋亡以及炎症和抗氧化反应的基因的表达，这些基因与 SCI 发病机制有关。在 H ₂ O ₂- 诱导细胞损伤模型，miR-324-5p 沉默挽救了 PC12 细胞凋亡升高。最后，miR-324-5p 直接靶向 NAD 依赖性蛋白去乙酰化酶 sirtuin-1 (Sirt1) 的 3'-非翻译区，并负调控参与 SCI 的抗炎蛋白 Sirt1 的水平。Sirt1 的沉默加重了 SCI 并挽救了 miR-324-5p 下调对大鼠的影响。总体而言，我们的研究结果表明，miR-324-5p 的沉默减轻了动物运动的丧失，同时通过 Sirt1 介导了与 SCI 发病机制相关的几个退行性过程，这可能为 SCI 治疗提供线索。