中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (9): 2022-2028.doi: 10.4103/1673-5374.335164

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

microRNA-101a-3p模拟物可减轻脊髓缺血再灌注损伤

  

  • 出版日期:2022-09-15 发布日期:2022-03-05

MicroRNA-101a-3p mimic ameliorates spinal cord ischemia/reperfusion injury

Zai-Li Zhang, Dan Wang, Feng-Shou Chen*   

  1. Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2022-09-15 Published:2022-03-05
  • Contact: Feng-Shou Chen, MD, PhD, haoxiu19881988@126.com.

摘要:

miR-101a-3p可在多种器官和组织中表达,并在多种疾病中发挥调节作用,但其在脊髓缺血再灌注损伤中的作用尚不明确。实验夹闭主动脉弓14min再灌注24h建立了脊髓缺血再灌注损伤大鼠模型,24h后发现L4-6脊髓组织中miR-101a-3p的表达明显下降,而MYCN表达则显著上调。同时双荧光素酶报告基因检测结果显示miR-101a-3p可靶向MYCN。L4-6脊髓组织中与神经元共定位的MYCN免疫阳性反应也显著增加。但是损伤前24h鞘内注射miR-101a-3p模拟物则可降低了L4-6脊髓组织中MYCN、p53、caspase-9和白细胞介素1β的表达,减少L4-6脊髓组织中p53免疫阳性反应、MYCN/NeuN双阳性细胞数量以及细胞凋亡,并增加大鼠的Tarlov评分。因此提示,miR-101a-3p可通过抑制MYCN和p53信号通路来改善脊髓缺血再灌注损伤诱导的神经细胞凋亡和炎症反应,因而miR-101a-3p可能是一种潜在的治疗方法。

https://orcid.org/0000-0001-7897-8680 (Zai-Li Zhang)

关键词: 脊髓缺血再灌注损伤, microRNA-101a-3p, MYCN, p53, caspase-9, 白细胞介素1β, 神经细胞, 细胞凋亡, 炎症

Abstract: miR-101a-3p is expressed in a variety of organs and tissues and plays a regulatory role in many diseases, but its role in spinal cord ischemia/reperfusion injury remains unclear. In this study, we established a rat model of spinal cord ischemia/reperfusion injury by clamping the aortic arch for 14 minutes followed by reperfusion for 24 hours. Results showed that miR-101a-3p expression in L4–L6 spinal cord was greatly decreased, whereas MYCN expression was greatly increased. Dual-luciferase reporter assay results showed that miR-101a-3p targeted MYCN. MYCN immunoreactivity, which was primarily colocalized with neurons in L4–L6 spinal tissue, greatly increased after spinal cord ischemia/reperfusion injury. However, intrathecal injection of an miR-101a-3p mimic within 24 hours before injury decreased MYCN, p53, caspase-9 and interleukin-1β expression, reduced p53 immunoreactivity, reduced the number of MYCN/NeuN-positive cells and the number of necrotic cells in L4–L6 spinal tissue, and increased Tarlov scores. These findings suggest that the miR-101a-3p mimic improved spinal ischemia/reperfusion injury-induced nerve cell apoptosis and inflammation by inhibiting MYCN and the p53 signaling pathway. Therefore, miR-101a-3p mimic therapy may be a potential treatment option for spinal ischemia/reperfusion injury. 

Key words: apoptosis, caspase-9, inflammation, interleukin-1β, microRNA-101a-3p, MYCN, nerve cells, p53, spinal cord ischemia/reperfusion injury