Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture
Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture
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DOI：
10.1016/j.neuint.2009.04.012
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发表时间：
2009-11-01
影响因子：
4.2
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Chan, Wing-Sai;Durairajan, Siva Sundara Kumar;Li, Min
帕金森病（PD）是由黑质多巴胺能神经元的进行性变性引起的。氧化应激和神经退行性变可能参与帕金森病的发病机制。本研究从治疗神经退行性疾病的中药黄芪干根中提取黄芪甲苷（Astragaloside IV, AS-IV），研究其对实验性帕金森病多巴胺能神经元的保护作用。通过检测AS-IV对原代培养的6-羟多巴胺（6-OHDA）诱导的多巴胺能神经元丢失的影响，我们发现AS-IV预处理显著且剂量依赖性地减弱了6-OHDA诱导的多巴胺能神经元丢失。神经元纤维长度研究表明，在6-OHDA培养的培养物中，观察到大量神经元细胞死亡并伴有退化的神经元，而在AS-IV共处理中，大多数多巴胺能神经元被观察到完整并发芽。流式细胞术分析显示，AS-IV对6-羟多巴胺诱导的多巴胺能神经元变性的酪氨酸水解酶（TH）免疫阳性细胞有明显的剂量依赖性的拯救作用。双免疫荧光显示，100和200 μ M浓度的AS-IV单独处理可提高TH和NOS（亚硝酸盐氧化物合成酶）的免疫反应活性；然而，AS-IV对6-OHDA处理的神经细胞TH和NOS免疫阳性细胞的保护作用仅在100 μ m浓度下可见，这表明AS-IV对6-OHDA诱导的多巴胺能神经元变性具有保护作用。除神经保护作用外，AS-IV单用可促进神经突生长，提高多巴胺能神经元TH和NOS免疫反应。AS-IV对多巴胺能神经元具有特异性的神经保护和神经芽化作用，在PD的治疗中具有潜在的治疗潜力。2009爱思唯尔有限公司版权所有。
Parkinson's disease (PD) is caused by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In the present study, Astragaloside IV (AS-IV) extracted from the dried root of Astragalus membranaceus, a well-known Chinese medicine used for the treatment of neurodegenerative diseases, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. By examining the effect of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in primary nigral culture, we found that AS-IV pretreatment significantly and dose-dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal fiber length studies showed that massive neuronal cell death with degenerated neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co-treatments most dopaminergic neurons were seen to be intact and sprouting. In flow cytometric analysis, AS-IV resulted in a marked and dose-dependent rescue in tyrosine hydrolase (TH)-immunopositive cells from 6-OHDA-induced degeneration of dopaminergic neurons. Double immunofluorescence revealed that AS-IV treatment alone at concentrations of 100 and 200 mu M increased the level of TH and NOS (nitrite oxide synthase) immunoreactivities; however, the protective effect of AS-IV on TH and NOS immunopositive cells in 6-OHDA treated nigral cell cultures was only seen at a concentration of 100 mu M. These findings show that AS-IV can protect dopaminergic neurons against 6-OHDA-induced degeneration. Besides the neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH and NOS immunoreactive of dopaminergic neurons. The neuroprotective and neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has therapeutic potential in the treatment of PD. (C) 2009 Elsevier Ltd. All rights reserved.