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胞磷胆碱对6-羟基多巴胺损伤大鼠及6-羟基多巴胺处理的SH-SY5Y人神经母细胞瘤细胞的神经保护作用。

Neuroprotective effect of citicoline in 6-hydroxydopamine-lesioned rats and in 6-hydroxydopamine-treated SH-SY5Y human neuroblastoma cells.

作者信息

Barrachina Marta, Domínguez Isabel, Ambrosio Santiago, Secades Julio, Lozano Rafael, Ferrer Isidro

机构信息

Unitat de Neuropatologia, Departament de Biologia Cellular i Anatomia Patològica, Universitat de Barcelona, Campus de Bellvitge, c/Feixa Llarga s/n, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.

出版信息

J Neurol Sci. 2003 Nov 15;215(1-2):105-10. doi: 10.1016/s0022-510x(03)00204-1.

Abstract

Citicoline (CDP-choline or cytidine 5'-diphosphocholine) has been used as a therapeutic agent in combination with levodopa in the treatment of Parkinson's disease (PD). The present study examines the effects of citicoline by using validated in vivo and in vitro models. Citicoline reduces the cytotoxic effect of 6-hydroxydopamine (6-OHDA)-treated human dopaminergic SH-SY5Y neuroblastoma cells as measured cellular redox activity with 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) and increases the levels of reduced glutathione (GSH), a major antioxidant agent. Moreover, citicoline (500 mg/kg i.p.) administered for 7 days ameliorates functional behaviour by significantly reducing the number of apomorphine-induced contralateral rotations in 6-OHDA rats. Finally, citicoline significantly attenuates substantia nigra (SN) dopaminergic cell dropout and tyrosine hydroxylase immunoreactivity in the ipsilateral striatum in rats injected intrastriatally with 6-hydroxydopamine (6-OHDA).

摘要

胞磷胆碱(CDP - 胆碱或胞苷5'-二磷酸胆碱)已被用作与左旋多巴联合治疗帕金森病(PD)的治疗药物。本研究通过使用经过验证的体内和体外模型来研究胞磷胆碱的作用。胞磷胆碱可降低6 - 羟基多巴胺(6 - OHDA)处理的人多巴胺能SH - SY5Y神经母细胞瘤细胞的细胞毒性作用,这是通过用3 - [4,5 - 二甲基噻唑 - 2 - 基] - 2,5 - 二苯基四氮唑溴盐(MTT)测量细胞氧化还原活性来评估的,并且可提高主要抗氧化剂还原型谷胱甘肽(GSH)的水平。此外,腹腔注射胞磷胆碱(500 mg/kg)持续7天可通过显著减少6 - OHDA大鼠中阿扑吗啡诱导的对侧旋转次数来改善功能行为。最后,在脑内注射6 - 羟基多巴胺(6 - OHDA)的大鼠中,胞磷胆碱可显著减轻黑质(SN)多巴胺能细胞缺失以及同侧纹状体中酪氨酸羟化酶免疫反应性。

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