ABSTRACT

Background: Spinal cord injury (SCI) has high disability rate and low cure rate, which frustrates the patients and brings a heavy burden to their families. This study aimed to explore whether NF-κB1 could induce the expression of LINC00665 and form a feedback loop with miR-34a-5p to regulate inflammation and apoptosis of neurons. Results: Basso, Beattie, and Bresnahan (BBB) scoring was decreased, damage for spinal cord tissue was aggravated and neuron number was decreased in SCI rats. The levels of TNF-α, IL-1β and IL-6 in serum and the expression of LINC00665 and NF-κB1 in spinal cord tissues were all increased in SCI rats. After LPS induction, PC12 cell viability was decreased. The expression of LINC00665 and NF-κB1 in LPS-induced PC12 cells was increased, which was partially reversed by BAY11-7082 (NF-κB inhibitor). Inhibition of LINC00665 improved cell viability, suppressed apoptosis and inflammation and down-regulated the NF-κB1 expression in LPS-induced PC12 cells. Furthermore, miR-34a-5p expression was decreased in LPS-induced PC12 cells, which could be promoted by inhibition of LINC00665. miR-34a-5p inhibitor restrained the effect of inhibition of LINC00665 on NF-κB1 expression in LPS-induced PC12 cells. Conclusion: inhibition of LINC00665 improved cell viability, suppressed apoptosis and inflammation in LPS-induced PC12 cells, and the NF-κB1/LINC00665/miR-34a-5ploop might be a useful therapeutic target in SCI treatment.

摘要

背景：脊髓损伤（SCI）的残障率高，治愈率低，这使患者感到沮丧，并给他们的家庭带来沉重负担。这项研究旨在探讨NF-κB1是否可以诱导LINC00665的表达并与miR-34a-5p形成反馈环来调节神经元的炎症和凋亡。结果：SCI大鼠的Basso，Beattie和Bresnahan（BBB）得分降低，脊髓组织损伤加重，神经元数量减少。SCI大鼠血清中TNF-α，IL-1β和IL-6水平以及脊髓组织中LINC00665和NF-κB1的表达均升高。LPS诱导后，PC12细胞活力降低。LPS诱导的PC12细胞中LINC00665和NF-κB1的表达增加，而BAY11-7082（NF-κB抑制剂）可部分逆转该表达。抑制LINC00665可改善细胞活力，抑制细胞凋亡和炎症，并下调LPS诱导的PC12细胞中NF-κB1的表达。此外，miR-34a-5p表达在LPS诱导的PC12细胞中降低，这可能是由于抑制LINC00665所促进。结论：抑制LINC00665可提高LPS诱导的PC12细胞的细胞活力，抑制细胞凋亡和炎症反应，NF-κB1/ LINC00665 / miR-34a-5ploop可能是SCI治疗的有效靶点。