Department of Pain, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221108192. doi: 10.1177/09636897221108192.
Varicella zoster virus-induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by TRX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were decreased in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate TRX-induced PHN in mice.
水痘带状疱疹病毒引起的带状疱疹后神经痛(PHN)可以通过有限的具有严重副作用的药物缓解。本研究旨在探讨 miR-199-3p 在介导小鼠 PHN 中的潜在分子机制。将 miR-199-3p 载体(模拟物/抑制剂)转染 293T 细胞。通过荧光素酶报告试验证实 miR-199-3p 与 MECP2 的靶关系。通过 TRX 注射建立 PHN 小鼠模型。使用 Hargreaves 测试和 Von Frey 测试评估动物行为。使用 Western blot 进行蛋白质分析,使用定量逆转录聚合酶链反应进行信使 RNA 定量。使用 ELISA 测定血清中炎症介质的水平。树脂毒素诱导的 PHN 小鼠的爪退缩潜伏期(PWL)和机械退缩阈值(MWT)降低。在 PHN 小鼠中发现下调的 miR-199-3p 和上调的 MECP2。上调的 miR-199-3p 增加了 PWL 和 MWT,但抑制了 PHN 小鼠中的 MECP2。此外,增加的 miR-199-3p 抑制了促炎指标并激活了抗炎介质。还发现 MECP2 是 miR-199-3p 的靶标。进一步的研究表明,miR-199-3p 通过靶向 MECP2 增强 PWL 和 MWT,并通过靶向 MECP2 来抑制炎症反应。miR-199-3p 通过靶向 MECP2 调节炎症反应,从而缓解 TRX 诱导的小鼠 PHN。