Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Bioengineered. 2021 Dec;12(1):4794-4804. doi: 10.1080/21655979.2021.1957071.
Dexmedetomidine (Dex) has been reported to exhibit neuroprotective effects through various regulatory mechanisms. This study aims to investigate the role and molecular mechanism of SNHG11 in Dex-mediated neuroprotection. The ischemic stroke (IS) model was established by middle cerebral artery occlusion (MCAO) and by oxygen-glucose deprivation and reperfusion (OGD/R)-treated SH-SY5Y. SNHG11 was highly expressed after OGD/R, and Dex improved OGD/R-induced neurological injury. Additionally, Dex reversed the effects of SNHG11 on OGD/R-induced neurological injury. Furthermore, we found that SNHG11 upregulated vascular endothelial growth factor A (VEGFA) expression by targeting miR-324-3p. Through rescue assays, it was confirmed that SNHG11 regulated OGD/R-induced neurological injury through increasing VEGFA expression. At last, Dex was also discovered to improve neurological injury through regulating SNHG11 in the rat model. In conclusion, our work demonstrated that Dex improved OGD/R-induced neurological injury via SNHG11/miR-324-3p/VEGFA axis. These findings may offer a novel therapeutic strategy for IS treatment.
地塞米松（Dex）通过多种调节机制显示出神经保护作用。本研究旨在探讨 SNHG11 在 Dex 介导的神经保护中的作用和分子机制。通过大脑中动脉闭塞（MCAO）和氧葡萄糖剥夺和再灌注（OGD/R）处理的 SH-SY5Y 建立缺血性中风（IS）模型。OGD/R 后 SNHG11 表达水平升高，Dex 改善了 OGD/R 诱导的神经损伤。此外，Dex 逆转了 SNHG11 对 OGD/R 诱导的神经损伤的影响。进一步研究发现，SNHG11 通过靶向 miR-324-3p 上调血管内皮生长因子 A（VEGFA）的表达。通过挽救实验证实，SNHG11 通过增加 VEGFA 的表达来调节 OGD/R 诱导的神经损伤。最后，还发现 Dex 通过调节大鼠模型中的 SNHG11 来改善神经损伤。总之，我们的工作表明 Dex 通过 SNHG11/miR-324-3p/VEGFA 轴改善了 OGD/R 诱导的神经损伤。这些发现可能为 IS 的治疗提供一种新的治疗策略。
