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神经妥乐平促进雪旺细胞分化和髓磷脂再生在大鼠溶血磷脂酰胆碱诱导的脱髓鞘模型中。

Neurotropin Accelerates the Differentiation of Schwann Cells and Remyelination in a Rat Lysophosphatidylcholine-Induced Demyelination Model.

机构信息

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Department of Orthopaedic Surgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, Hyogo 660-0064, Japan.

出版信息

Int J Mol Sci. 2018 Feb 8;19(2):516. doi: 10.3390/ijms19020516.

Abstract

Neurotropin (NTP), a non-protein extract of inflamed rabbit skin inoculated with vaccinia virus, is clinically used for the treatment of neuropathic pain in Japan and China, although its effect on peripheral nerve regeneration remains to be elucidated. The purpose of this study was to investigate the effects of NTP on Schwann cells (SCs) in vitro and in vivo, which play an important role in peripheral nerve regeneration. In SCs, NTP upregulated protein kinase B (AKT) activity and Krox20 and downregulated extracellular signal-regulated kinase1/2 activity under both growth and differentiation conditions, enhanced the expression of myelin basic protein and protein zero under the differentiation condition. In a co-culture of dorsal root ganglion neurons and SCs, NTP accelerated myelination of SCs. To further investigate the influence of NTP on SCs in vivo, lysophosphatidylcholine was injected into the rat sciatic nerve, leading to the focal demyelination. After demyelination, NTP was administered systemically with an osmotic pump for one week. NTP improved the ratio of myelinated axons and motor, sensory, and electrophysiological function. These findings reveal novel effects of NTP on SCs differentiation in vitro and in vivo, and indicate NTP as a promising treatment option for peripheral nerve injuries and demyelinating diseases.

摘要

神经妥乐平(NTP)是一种从接种牛痘病毒的兔炎性皮肤中提取的非蛋白物质,在日本和中国临床上用于治疗神经性疼痛,但其对周围神经再生的影响仍需阐明。本研究旨在探讨 NTP 在体外和体内对雪旺细胞(SCs)的作用,SCs 在周围神经再生中起重要作用。在生长和分化条件下,NTP 可上调蛋白激酶 B(AKT)活性和Krox20,下调细胞外信号调节激酶 1/2 活性,在分化条件下可增强髓鞘碱性蛋白和蛋白零的表达。在背根神经节神经元和SCs 的共培养中,NTP 可加速SCs 的髓鞘形成。为了进一步研究 NTP 对体内SCs 的影响,向大鼠坐骨神经内注射溶血磷脂酰胆碱导致局部脱髓鞘。脱髓鞘后,通过渗透泵系统给予 NTP 治疗 1 周。NTP 改善了有髓轴突的比例以及运动、感觉和电生理功能。这些发现揭示了 NTP 对体外和体内SCs 分化的新作用,并表明 NTP 可能成为治疗周围神经损伤和脱髓鞘疾病的有前途的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc57/5855738/7bd356611a93/ijms-19-00516-g001a.jpg

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