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丁香酚对癫痫锂-匹罗卡品模型的影响:行为学、组织学及分子变化

Effect of eugenol on lithium-pilocarpine model of epilepsy: behavioral, histological, and molecular changes.

作者信息

Joushi Sara, Salmani Mahmoud Elahdadi

机构信息

School of Biology, Damghan University, Damghan, Iran.

Institute of Biological Sciences, Damghan University, Damghan, Iran.

出版信息

Iran J Basic Med Sci. 2017 Jul;20(7):745-752. doi: 10.22038/IJBMS.2017.9004.

Abstract

OBJECTIVES

Epilepsy establishment gives rise to biochemical and morphological changes in the hippocampus. Oxidative stress, morphological changes, and mossy fiber sprouting (MFS) in the hippocampus underpin the epilepsy establishment. Eugenol is the main component of the essential oil extracted from cloves with the potential to modulate neuronal excitability. Therefore, we investigated the effect of eugenol on convulsive behavior, oxidative stress, and histological changes of the hippocampus in lithium-pilocarpine model of epilepsy.

MATERIALS AND METHODS

Male Wistar rats weighing 220-250 g were divided into 4 groups; Control, Pilocarpine, Eugenol-Pilocarpine, and Eugenol. Oxidative stress markers were assayed by a biochemical method. Nissl and Timm staining were used to show neuronal survival and MFS, respectively. Behavioral convulsions were evaluated using the modified Racine scale.

RESULTS

Eugenol decreased seizure stage and duration as well as mortality. Neuronal numbers were preserved by eugenol treatment in epileptic animals, while eugenol alone reduced the number by itself in all hippocampal sub-regions including DG, CA3, and CA1. Furthermore, eugenol alone increased MDA, GPx and SOD markers, while it increased MDA not only in combined treatment with pilocarpine but also in pilocarpine-treated animals. In contrast to MFS enhancement in naïve animals, eugenol partially reversed the MFS enhancement induced by pilocarpine.

CONCLUSION

Eugenol could prevent behavioral convulsions and show neuroprotective effects through increasing neuronal survival probably by decreasing MFS and increasing the GPx antioxidant marker.

摘要

目的

癫痫的形成会导致海马体发生生化和形态学变化。海马体中的氧化应激、形态学变化和苔藓纤维发芽(MFS)是癫痫形成的基础。丁香酚是从丁香中提取的挥发油的主要成分,具有调节神经元兴奋性的潜力。因此,我们研究了丁香酚对癫痫锂-匹罗卡品模型中惊厥行为、氧化应激和海马体组织学变化的影响。

材料与方法

将体重220-250g的雄性Wistar大鼠分为4组;对照组、匹罗卡品组、丁香酚-匹罗卡品组和丁香酚组。采用生化方法检测氧化应激标志物。分别用尼氏染色和Timm染色显示神经元存活和苔藓纤维发芽。使用改良的Racine评分评估行为惊厥。

结果

丁香酚降低了癫痫发作阶段、持续时间以及死亡率。丁香酚处理可使癫痫动物的神经元数量得以保留,而单独使用丁香酚会使包括齿状回(DG)、海马体CA3区和CA1区在内的所有海马亚区的神经元数量减少。此外,单独使用丁香酚会增加丙二醛(MDA)、谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)标志物,而它不仅在与匹罗卡品联合处理时增加MDA,在匹罗卡品处理的动物中也会增加MDA。与未处理动物中苔藓纤维发芽增强相反,丁香酚部分逆转了匹罗卡品诱导的苔藓纤维发芽增强。

结论

丁香酚可能通过减少苔藓纤维发芽和增加GPx抗氧化标志物来提高神经元存活率,从而预防行为惊厥并显示出神经保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38b8/5569590/c29c8d9aa7c7/IJBMS-20-745-g001.jpg

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