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研究催产素和利拉鲁肽对长春新碱诱导的大鼠神经病变的治疗潜力。

The investigation of therapeutic potential of oxytocin and liraglutide on vincristine-induced neuropathy in rats.

机构信息

Department of Physiology, Katip Çelebi University School of Medicine, Izmir, Turkey.

Department of Internal Medicine, Ege University School of Medicine, Izmir, Turkey.

出版信息

J Biochem Mol Toxicol. 2020 Jan;34(1):e22415. doi: 10.1002/jbt.22415. Epub 2019 Nov 4.

Abstract

The aim of this study was to assess the therapeutic potential of oxytocin and liraglutide (LIR), a GLP-1 analogue, in a rat model of vincristine-induced neuropathy. Rats were injected with vincristine (VCR) at a dose of 4 mg/kg twice a week for 5 weeks. The VCR-administered rats were divided into three groups and received saline, oxytocin, or liraglutide simultaneously with VCR. After the treatment period, electrophysiological, biochemical, histological, and immunohistochemical investigations were performed. Electromyography (EMG) recordings demonstrated significant alterations in the VCR + saline group (p < .001). Also, motor performance was decreased in the VCR + saline group (p < .05). Histologically, the axonal diameter was decreased in all groups. VCR + saline group showed significantly increased lipid peroxidation and decreased nerve growth factor (NGF) expression. However, the administration of oxytocin and liraglutide significantly prevented the EMG alterations, lipid peroxidation, and reduction in neuronal NGF expression. On the basis of these findings, oxytocin and liraglutide may be considered as potential agents for the prevention of VCR-induced neuropathy.

摘要

本研究旨在评估催产素和利拉鲁肽(LIR),一种 GLP-1 类似物,在长春新碱诱导的神经病变大鼠模型中的治疗潜力。大鼠每周两次接受 4mg/kg 的长春新碱(VCR)注射,共 5 周。接受 VCR 注射的大鼠分为三组,同时接受生理盐水、催产素或利拉鲁肽治疗。治疗期结束后,进行电生理学、生物化学、组织学和免疫组织化学研究。肌电图(EMG)记录显示 VCR+生理盐水组发生显著变化(p<.001)。此外,VCR+生理盐水组的运动性能下降(p<.05)。组织学上,所有组的轴突直径均减小。VCR+生理盐水组的脂质过氧化明显增加,神经生长因子(NGF)表达减少。然而,催产素和利拉鲁肽的给药显著预防了 EMG 改变、脂质过氧化和神经元 NGF 表达减少。基于这些发现,催产素和利拉鲁肽可能被认为是预防长春新碱诱导的神经病变的潜在药物。

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