MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat.
MiR-128-3p Alleviates Spinal Cord Ischemia/Reperfusion Injury Associated Neuroinflammation and Cellular Apoptosis via SP1 Suppression in Rat.
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MiR-128-3p 通过抑制 SP1 减轻大鼠脊髓缺血/再灌注损伤相关的神经炎症和细胞凋亡
DOI：
10.3389/fnins.2020.609613
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发表时间：
2020
影响因子：
4.3
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Wang D;Chen F;Fang B;Zhang Z;Dong Y;Tong X;Ma H
背景脊髓缺血再灌注（I/R）损伤引起的神经炎症和细胞凋亡导致神经功能障碍。已有证据表明，MicroRNAs在脊髓I/R损伤的发病机制中具有重要作用。本文评估miR-128-3p是否通过调节特异性蛋白1 （SP1）参与脊髓I/R损伤。方法采用主动脉弓闭塞14 min的方法建立大鼠脊髓I/R损伤模型。然后，通过双荧光素酶报告基因检测miR-128-3p与SP1的相互作用。接下来，在鞘内注射miR-128-3p模拟物和抑制剂，以及腺病毒递送的SP1特异性shRNA，以评估miR-128-3p和SP1对脊髓I/R损伤大鼠的影响。Western blotting检测SP1、Bax、Bcl-2在I/R损伤脊髓组织中的表达水平，ELISA检测IL-1β、TNF-α、IL-6的表达水平。采用Tarlov评分检测后肢运动功能。Evans蓝（EB）染色外渗检测血脊髓屏障（BSCB）通透性。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色评估神经元凋亡。结果I/R后大鼠脊髓组织标本中MiR-128-3p表达降低，SP1表达增加。SP1被确定为miR-128-3p的靶标，并被miR-128-3p下调。MiR-128-3p过表达或SP1沉默可减轻I/ r诱导的神经炎症和细胞凋亡，提高Tarlov评分，而MiR-128-3p抑制剂预处理加重了上述损伤。结论miR-128-3p过表达部分通过下调SP1调控来保护脊髓I/R损伤时神经元的炎症和凋亡。
Background Neuroinflammation and cellular apoptosis caused by spinal cord ischemia/reperfusion (I/R) injury result in neurological dysfunction. MicroRNAs (miRs) have crucial functions in spinal cord I/R injury pathogenesis according to previous evidences. Herein, whether miR-128-3p contributes to spinal cord I/R injury by regulating specificity protein 1 (SP1) was assessed. Methods A rat model of spinal cord I/R injury was established by occluding the aortic arch for 14 min. Then, miR-128-3p’s interaction with SP1 was detected by dual-luciferase reporter assays. Next, miR-128-3p mimic and inhibitor, as well as adenovirus-delivered shRNA specific for SP1 were injected intrathecally for assessing the effects of miR-128-3p and SP1 on rats with spinal cord I/R injury. SP1, Bax and Bcl-2 expression levels in I/R injured spinal cord tissues were evaluated by Western blotting, while IL-1β, TNF-α, and IL-6 were quantitated by ELISA. Tarlov scores were obtained to detect hind-limb motor function. Evans blue (EB) dye extravasation was utilized to examine blood–spinal cord barrier (BSCB) permeability. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining was performed for neuronal apoptosis assessment. Results MiR-128-3p expression was decreased, while SP1 amounts were increased in rat spinal cord tissue specimens following I/R. SP1 was identified as a miR-128-3p target and downregulated by miR-128-3p. MiR-128-3p overexpression or SP1 silencing alleviated I/R-induced neuroinflammation and cell apoptosis, and improved Tarlov scores, whereas pretreatment with miR-128-3p inhibitor aggravated the above injuries. Conclusion Overexpression of miR-128-3p protects neurons from neuroinflammation and apoptosis during spinal cord I/R injury partially by downregulating SP1.
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