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从双带扁蛛(园蛛科:蜘蛛目)毒液中分离出的化合物parawixin 10对海马内注射NMDA的大鼠的神经保护活性。

Neuroprotective activity of parawixin 10, a compound isolated from Parawixia bistriata spider venom (Araneidae: Araneae) in rats undergoing intrahippocampal NMDA microinjection.

作者信息

Fachim Helene Aparecida, Mortari Marcia Renata, Gobbo-Netto Leonardo, Dos Santos Wagner Ferreira

机构信息

Department of Biology, Neurobiology and Venoms Laboratory, FFCLRP, Brazil ; Institute of Neuroscience and Behavior, INeC-Ribeirão Preto, São Paulo, Brazil.

Department of Physiological Sciences, Laboratory of Neuropharmacology, Institute of Biological Sciences, University of Brasilia, Campus Universitário Darcy Ribeiro, 70910-900 Brasília, DF, Brazil.

出版信息

Pharmacogn Mag. 2015 Jul-Sep;11(43):579-85. doi: 10.4103/0973-1296.160450.

Abstract

BACKGROUND

Parawixia bistriata is a semi-colonial spider found mainly in southeastern of Brazil. Parawixin 10 (Pwx 10) a compound isolated from this spider venom has been demonstrated to act as neuroprotective in models of injury regulating the glutamatergic neurotransmission through glutamate transporters.

OBJECTIVES

The aim of this work was to evaluate the neuroprotective effect of Pwx 10 in a rat model of excitotoxic brain injury by N-methyl-D-aspartate (NMDA) injection.

MATERIAL AND METHODS

Male Wistar rats have been used, submitted to stereotaxic surgery for saline or NMDA microinjection into dorsal hippocampus. Two groups of animals were treated with Pwx 10. These treated groups received a daily injection of the Pwx 10 (2.5 mg/μL) in the right lateral ventricle into rats pretreated with NMDA, always at the same time, each one starting the treatment 1 h or 24 h. Nissl staining was performed for evaluating the extension and efficacy of the NMDA injury and the neuroprotective effect of Pwx 10.

RESULTS

The treatment with Pwx 10 showed neuroprotective effect, being most pronounced when the compound was administrated from 1 h after NMDA in all hippocampal subfields analyzed (CA1, CA3 and hilus).

CONCLUSION

These results indicated that Pwx 10 may be a good template to develop therapeutic drugs for treating neurodegenerative diseases, reinforcing the importance of continuing studies on its effects in the central nervous system.

摘要

背景

双带扁蛛是一种半群居性蜘蛛,主要分布在巴西东南部。从这种蜘蛛毒液中分离出的化合物Parawixin 10(Pwx 10)已被证明在损伤模型中具有神经保护作用,可通过谷氨酸转运体调节谷氨酸能神经传递。

目的

本研究旨在评估Pwx 10在N-甲基-D-天冬氨酸(NMDA)注射所致兴奋性毒性脑损伤大鼠模型中的神经保护作用。

材料与方法

选用雄性Wistar大鼠,接受立体定向手术,向背侧海马注射生理盐水或NMDA。两组动物接受Pwx 10治疗。这些治疗组在给用NMDA预处理的大鼠右侧脑室每日注射Pwx 10(2.5 mg/μL),时间固定,每组分别在1小时或24小时开始治疗。采用尼氏染色评估NMDA损伤的范围和效果以及Pwx 10的神经保护作用。

结果

Pwx 10治疗显示出神经保护作用,在分析的所有海马亚区(CA1、CA3和齿状回)中,从NMDA注射后1小时开始给予该化合物时,神经保护作用最为明显。

结论

这些结果表明,Pwx 10可能是开发治疗神经退行性疾病治疗药物的良好模板,这进一步凸显了继续研究其在中枢神经系统中作用的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6913/4522846/38e0f24789ea/PM-11-579-g001.jpg

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