Department of Neurology, Taizhou People's Hospital, No. 366 Taihu Road, Hailing District, Taizhou, 225300, Jiangsu, China.
Department of ICU, Taizhou People's Hospital, Taizhou, 225300, Jiangsu, China.
Genes Genomics. 2019 Jun;41(6):713-721. doi: 10.1007/s13258-019-00802-0. Epub 2019 Mar 8.
Neuropathic pain (NP) is one of the main challenges towards NP syndrome treatment. miR-340-5p exhibit different expression levels in NP models. Its effects on NP remained unclear. The objective of this study was to explore the potential regulation mechanisms of miR-340-5p in NP.
Rat model of chronic constriction injury (CCI) was established to induce NP in vivo. NP levels were assessed using mechanical withdrawal threshold (MWT). The inflammation response in CCI rats were determined by HE staining and ELISA assay. The target genes of miR-340-5p were verified by luciferase report assays.
In CCI rats, level of miR-340-5p was down-regulated both in spinal cord tissues and isolated microglial cells. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were decreased in CCI rats, which were restored upon miR-340-5p overexpression. miR-340-5p overexpression also decreased inflammation as well as expression levels of COX-2, IL-1β, TNF-α and IL-6 in CCI rats. Luciferase report assays revealed Rap1A was a target gene of miR-340-5p in the experimental model. Elevated miR-340-5p decreased Rap1A expression level in vitro and in vivo. Overexpression of Rap1A protein restored expression levels of COX-2, IL-1β, TNF-α and IL-6, reduced the PWT and PWL and increased inflammation response in CCI rats.
miR-340-5p alleviated CCI-induced NP by targeting Rap1A. miR-340-5p and Rap1A may be the potential treatment targets for NP therapeutics.
神经性疼痛（NP）是 NP 综合征治疗的主要挑战之一。miR-340-5p 在 NP 模型中表现出不同的表达水平。其对 NP 的影响尚不清楚。本研究旨在探讨 miR-340-5p 在 NP 中的潜在调节机制。
建立大鼠慢性缩窄性损伤（CCI）模型，在体内诱导 NP。采用机械撤足阈值（MWT）评估 NP 水平。通过 HE 染色和 ELISA 测定 CCI 大鼠的炎症反应。通过荧光素酶报告试验验证 miR-340-5p 的靶基因。
在 CCI 大鼠中，脊髓组织和分离的小胶质细胞中 miR-340-5p 的水平均下调。CCI 大鼠的足撤回阈值（PWT）和足撤回潜伏期（PWL）降低，miR-340-5p 过表达后恢复。miR-340-5p 过表达还降低了 CCI 大鼠的炎症以及 COX-2、IL-1β、TNF-α 和 IL-6 的表达水平。荧光素酶报告试验显示，Rap1A 是实验模型中 miR-340-5p 的靶基因。升高的 miR-340-5p 降低了体外和体内 Rap1A 的表达水平。Rap1A 蛋白的过表达恢复了 COX-2、IL-1β、TNF-α 和 IL-6 的表达水平，降低了 PWT 和 PWL，并增加了 CCI 大鼠的炎症反应。
miR-340-5p 通过靶向 Rap1A 缓解 CCI 诱导的 NP。miR-340-5p 和 Rap1A 可能是 NP 治疗的潜在治疗靶点。
