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嗅鞘细胞联合壳聚糖对抑制 P2X4 受体过表达介导的神经病理性疼痛的作用。

Effect of olfactory ensheathing cells combined with chitosan on inhibition of P2×4 receptor over-expression-mediated neuropathic pain.

机构信息

The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province, 343000, China.

The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province, 343000, China.

出版信息

Neurosci Lett. 2020 Mar 23;722:134859. doi: 10.1016/j.neulet.2020.134859. Epub 2020 Feb 22.

Abstract

Neuropathic pain (NPP) is a clinically refractory disease that causes pain to patients, and its treatment has always been an urgent problem to be solved. P2X4 receptor (P2X4R) plays a key role in the pathogenesis of neuropathic pain. Therefore, the aim of this studies to explore the effect of olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation on NPP caused by sciatic nerve injury in rats, and its relationship with the expression levels of P2X4R in the L4-5 dorsal root ganglion (DRG). In this study, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) was prepared, and the compatibility of CS and OECs was detected by MTT method. Animal model of chronic constrictive sciatic nerve injury (CCI) was made, OECs and OECs+CS were transplanted to the region surrounding the chronic sciatic nerve injury, and the difference between the two groups in the treatment of NPP was compared. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by using behavioral method. in situ hybridization and Western-blotting were used to detect the expression of P2X4R mRNA and protein in the DRG. These results showed that OECs had good biocompatibility with CS. Compared with the CCI, the MWT and TWL were significantly increased (P<0.05), the expression levels of P2X4R mRNA and protein in the OECs and OECs+CS group were significantly reduced (P<0.05). Compared with the OECs, the expression levels of P2X4R mRNA and protein in the OECs+CS group were significantly reduced (P<0.05), the MWT and TWL were significantly increased (P<0.05). We conclude that OECs+CS can better inhibit P2X4R over-expression-mediated NPP, and its therapeutic effect was superior to simple OECs transplantation, which may become another potential method for the treatment of NPP.

摘要

神经病理性疼痛(NPP)是一种临床难治性疾病,会给患者带来疼痛,其治疗一直是亟待解决的问题。P2X4 受体(P2X4R)在神经病理性疼痛的发病机制中起关键作用。因此,本研究旨在探讨嗅鞘细胞联合壳聚糖(OECs+CS)移植对大鼠坐骨神经损伤所致神经病理性疼痛的影响及其与 L4-5 背根神经节(DRG)中 P2X4R 表达水平的关系。

在本研究中,培养嗅鞘细胞(OECs),制备壳聚糖(CS),并通过 MTT 法检测 CS 与 OECs 的相容性。制作慢性缩窄性坐骨神经损伤(CCI)动物模型,将 OECs 和 OECs+CS 移植到慢性坐骨神经损伤区域,比较两组治疗 NPP 的差异。采用行为学方法测量机械退缩阈值(MWT)和热退缩潜伏期(TWL)。原位杂交和 Western-blotting 检测 DRG 中 P2X4R mRNA 和蛋白的表达。

结果表明,OECs 与 CS 具有良好的生物相容性。与 CCI 相比,MWT 和 TWL 显著增加(P<0.05),OECs 和 OECs+CS 组 P2X4R mRNA 和蛋白表达水平显著降低(P<0.05)。与 OECs 相比,OECs+CS 组 P2X4R mRNA 和蛋白表达水平显著降低(P<0.05),MWT 和 TWL 显著增加(P<0.05)。

我们得出结论,OECs+CS 能更好地抑制 P2X4R 过表达介导的 NPP,其治疗效果优于单纯 OECs 移植,可能成为治疗 NPP 的另一种潜在方法。

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