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首页> 外文期刊>Cell and Tissue Research >Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis
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Lithium alleviated spinal cord injury (SCI)-induced apoptosis and inflammation in rats via BDNF-AS/miR-9-5p axis

机译:通过BDNF-AS / miR-9-5P轴抑制脊髓损伤(SCI) - 诱导大鼠的细胞凋亡和炎症

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摘要

Spinal cord injury (SCI) is a major cause of paralysis, disability and even death in severe cases. Lithium has neuroprotective effects on SCI, while the underlying mechanisms remain obscure. In the present study, we established a SCI rat model, which subsequently received lithium treatment. Results displayed that lithium treatment improved the locomotor function recovery and reduced apoptosis by increasing anti-apoptotic molecule expression and decreasing pro-apoptotic factor expression in SCI rats. Furthermore, lithium treatment alleviated the inflammatory response by inactivating the nuclear factor-kappa B (NF-kappa B) pathway and inhibited the expression of lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) in SCI rats. Subsequent researches indicated that miR-9-5p was targeted and regulated by BDNF-AS. Lithium treatment rescued the upregulation of BDNF-AS expression and downregulation of miR-9-5p expression induced by H2O2 in SH-SY5Y cells. BDNF-AS overexpression or miR-9-5p interference attenuated the anti-apoptotic and anti-inflammatory effects of lithium chloride in SH-SY5Y cells that was damaged by H2O2 induction, revealing that lithium might act through the BDNF-AS/miR-9-5p axis. In vivo studies showed that the injection of BDNF-AS adenovirus vector or miR-9-5p inhibitor reversed the effects of lithium on the histologic morphology of spinal cord, motor function, inflammatory reaction and apoptosis in SCI rats, which was consistent with the results of in vitro studies. In conclusion, our data demonstrated that lithium reduced SCI-induced apoptosis and inflammation in rats via the BDNF-AS/miR-9-5p axis.
机译:脊髓损伤(SCI)是导致严重病例瘫痪、残疾甚至死亡的主要原因。锂对SCI有神经保护作用,但其潜在机制尚不清楚。在本研究中,我们建立了SCI大鼠模型,随后接受锂治疗。结果表明,锂处理通过增加SCI大鼠抗凋亡分子的表达和减少促凋亡因子的表达,促进了运动功能的恢复,减少了细胞凋亡。此外,锂治疗通过使核因子-κB(NF-κB)途径失活减轻了SCI大鼠的炎症反应,并抑制了lncRNA脑源性神经营养因子反义(BDNF-AS)的表达。随后的研究表明,miR-9-5p被BDNF-AS靶向和调控。锂处理挽救了H2O2诱导的SH-SY5Y细胞BDNF-AS表达上调和miR-9-5p表达下调。BDNF-AS过度表达或miR-9-5p干扰减弱了氯化锂对SH-SY5Y细胞的抗凋亡和抗炎作用,该细胞因H2O2诱导而受损,表明锂可能通过BDNF-AS/miR-9-5p轴发挥作用。体内研究表明,注射BDNF-AS腺病毒载体或miR-9-5p抑制剂可逆转锂对脊髓损伤大鼠脊髓组织形态学、运动功能、炎症反应和细胞凋亡的影响,这与体外研究结果一致。总之,我们的数据表明,锂通过BDNF-AS/miR-9-5p轴减少SCI诱导的大鼠凋亡和炎症。

著录项

  • 来源
    《Cell and Tissue Research》 |2021年第2期|共12页
  • 作者单位

    Xi An Jiao Tong Univ Affiliated Hosp 2 Coll Med Dept Orthopaed 157 Xiwu Rd Xian 710004;

    Xi An Jiao Tong Univ Affiliated Hosp 2 Coll Med Dept Orthopaed 157 Xiwu Rd Xian 710004;

    Xi An Jiao Tong Univ Affiliated Hosp 2 Coll Med Dept Orthopaed 157 Xiwu Rd Xian 710004;

    Xi An Jiao Tong Univ Affiliated Hosp 2 Coll Med Dept Orthopaed 157 Xiwu Rd Xian 710004;

    Xi An Jiao Tong Univ Affiliated Hosp 2 Coll Med Dept Orthopaed 157 Xiwu Rd Xian 710004;

    Xi An Jiao Tong Univ Affiliated Hosp 2 Coll Med Dept Orthopaed 157 Xiwu Rd Xian 710004;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Lithium; BDNF-AS; MiR-9-5p; Apoptosis; Inflammation; Spinal cord injury;

    机译:锂;BDNF-AS;miR-9-5p;细胞凋亡;炎症;脊髓损伤;

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