lncRNA-14238介导TLR-7信号通路参与腰椎间盘突出症模型大鼠痛觉高敏的机制研究

Lumbar disc herniation (LDH) is one of the most common causes of low back pain and sciatica. Studies have shown that the generation and maintenance of LDH pain is related to the central sensitization mechanism of the spinal cord. Recently, gene chip sequencing and qPCR assay showed that the expression of TLR-7 gene and its related lncRNA-14238 in spinal dorsal horn of LDH rats increased significantly, and the excitability of neurons in spinal dorsal horn was increased by patch clamp. Therefore, we hypothesize that lumbar disc herniation can increase the expression of TLR-7 in spinal dorsal horn, activate NF-kB, up-regulate lncRNA-14238, release inflammatory factors through transcriptional regulation, increase neuronal excitability and postsynaptic current, and ultimately produce LDH pain sensitization.TLR-7 and lncRNA-14238 shRNA lentiviruses will be used to study the role of TLR-7 in LDH pain sensitization and its regulation mechanism at the cellular, molecular and overall animal levels in order to find new targets for the treatment of lumbar disc herniation.

腰椎间盘突出症(lumbar disc herniation,LDH)是临床下腰痛和坐骨神经痛最常见的病因之一，已有研究显示LDH疼痛的产生和维持与脊髓的中枢敏化机制有关。我们近期进行基因芯片测序及qPCR实验检测，发现LDH大鼠脊髓背角中TLR-7基因及其相关的lncRNA-14238表达显著增加，膜片钳记录到脊髓背角神经元细胞的兴奋性增强。由此，我们提出研究假设：腰椎间盘突出症引起脊髓背角TLR-7的表达升高，激活NF-kB，上调lncRNA-14238，转录调控释放炎症因子，增加神经元兴奋性及突触后电流，最终产生LDH疼痛敏化。为证实上述研究假设，我们将分别应用TLR-7及lncRNA-14238 shRNA慢病毒进行研究，从细胞、分子及整体动物水平探讨TLR-7调控lncRNA-14238参与LDH疼痛敏化的作用及调控机制，以期为腰椎间盘突出症疼痛的治疗寻求新的靶点。

背景 腰椎间盘突出症(lumbar disc herniation, LDH)是临床下腰痛和坐骨神经痛最常见的病因之一 ，已有研究显示LDH疼痛的产生和维持与脊髓的中枢敏化机制有关。内容 TLR-7调控lncRNA-14238参与LDH疼痛敏化的分子机制 结果 基因芯片测序及Rt-PCR实验检测，发现LDH大鼠脊髓背角中TLR-7基因及其相关的lncRNA-14238表达显著增加，膜片钳记录到脊髓背角神经元细胞的兴奋性增强。应用TLR-7shRNA或者lncRNA-14238 shRNA慢病毒鞘内注射均能有效减轻LDH大鼠的疼痛行为学反应。科学意义 本研究从细胞、分子及整体动物水平探讨TLR-7调控lncRNA-14238在LDH 疼痛敏化中的作用及调控机制，为腰椎间盘突出症疼痛的治疗靶点提供新的理论依据。

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