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木立芦荟对大鼠铜诱导的帕金森病神经行为特征的神经保护潜力

Neuroprotective potential of Aloe arborescens against copper induced neurobehavioral features of Parkinson's disease in rat.

作者信息

Abbaoui Abdellatif, Hiba Omar El, Gamrani Halima

机构信息

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco.

Cadi Ayyad University, Faculty of Sciences Semlalia, Neurosciences, Pharmacology and Environment Unit, Marrakesh, Morocco; Chouaib Doukkali University, faculty of Sciences, Department of Biology, Morocco.

出版信息

Acta Histochem. 2017 Jun;119(5):592-601. doi: 10.1016/j.acthis.2017.06.003. Epub 2017 Jun 12.

DOI:10.1016/j.acthis.2017.06.003
PMID:28619286
Abstract

Copper (Cu) is an important trace element for the organism survival, which ensures the normal functioning of different biosystems. However, excessive levels of this heavy metal are responsible for profound physiological alterations including the central nervous system. Numerous findings sustain the involvement of heavy metals, as an environmental risk factor such as copper (Cu), in the neuropathology of Parkinson's disease (PD) which is a chronic neurodegenerative disorder that principally affects the motor system. The classic and evident symptoms of PD namely rigidity, tardiness of movement, and difficulty with walking, result from progressive dopaminergic neurons death within substantia nigra. Whereas, few pharmacological trials have shown a beneficial role against Cu neurotoxicity, Aloe arborescens is one of the powerful medicinal plants with an array of therapeutic effects. Thus, we aimed through the present study, to evaluate the impact of acute Cu intoxication (10μg/g B.W. i.p) for 3days on the dopaminergic system and locomotor performance, together with the possible restorative effect of oral administration of aqueous extract of Aloe arborescens gel (AEAAG) (200mg/kg B.W.). By means of immunohistochemistry, we noted, in the Cu intoxicated rats, a significant loss of TH (tyrosine hydroxylase) expression within substantia nigra compacta (SNc), ventral tegmental area (VTA) and the subsequent striatal outputs, those alterations were correlated to behavioral abnormalities such as a severe drop of locomotor performance. While AEAAG administration to Cu intoxicated rats showed a noticeable beneficial effect; this potential was featured by a complete recovery of the TH expression and locomotor behavior deficiencies in the intoxicated rats. The present investigation have brought, on the one hand, an experimental evidence of an altered dopaminergic innervations following Cu intoxication and on the other hand, a new pharmacological property of Aloe arborescens that may be used as a neuroprotective plant for neurodegenerative disorders, such as PD, touching the dopaminergic system trigged by heavy metals.

摘要

铜(Cu)是生物体生存所必需的重要微量元素,它能确保不同生物系统的正常运作。然而,这种重金属含量过高会导致包括中枢神经系统在内的深刻生理变化。大量研究结果表明,作为一种环境风险因素,重金属如铜(Cu)与帕金森病(PD)的神经病理学有关,帕金森病是一种主要影响运动系统的慢性神经退行性疾病。PD的典型明显症状,即僵硬、运动迟缓以及行走困难,是由黑质内多巴胺能神经元逐渐死亡导致的。尽管很少有药物试验显示对铜神经毒性有有益作用,但木立芦荟是一种具有一系列治疗作用的强效药用植物。因此,在本研究中,我们旨在评估急性铜中毒(腹腔注射10μg/g体重,持续3天)对多巴胺能系统和运动能力的影响,以及口服木立芦荟凝胶水提取物(AEAAG,200mg/kg体重)可能的恢复作用。通过免疫组织化学方法,我们发现,在铜中毒大鼠中,致密部黑质(SNc)、腹侧被盖区(VTA)以及随后的纹状体输出区域内酪氨酸羟化酶(TH)表达显著减少,这些改变与行为异常相关,如运动能力严重下降。而给铜中毒大鼠施用AEAAG显示出明显的有益效果;这种潜力表现为中毒大鼠的TH表达和运动行为缺陷完全恢复。本研究一方面提供了铜中毒后多巴胺能神经支配改变的实验证据,另一方面揭示了木立芦荟可能作为一种神经保护植物用于治疗如PD等涉及重金属引发多巴胺能系统的神经退行性疾病的新药理特性。

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