n-苯乙酰-l-丙氨酸乙酯鼻凝胶对多发性硬化症等效实验模型的神经保护作用

B. Burlaka, I. Belenichev, O. Nefedov, O. Aliyeva, N. Bukhtiyarova
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引用次数: 2

摘要

本研究的目的是研究我们研制的鼻剂型与n-苯乙酰-l-脯氨酸乙酯的比活性。实验以体重190 ~ 220 g的纯种大鼠260只为实验对象。以100 mg同源脊髓匀浆为基础,单次皮下接种含完全弗氏佐剂(CFA)的致脑混合物(EHM)诱导实验性过敏性脑脊髓炎(EAE);每只动物注射CFA 0.2 ml(死亡分枝杆菌含量5 mg/ml)和生理盐水0.2 ml。研究中有五组动物:1)完整的;2)对照组:未经EAE治疗,给予生理盐水溶液;3)接受基础治疗的EAE动物-甲基强的松龙(MP), 3.4 mg/kg,在生理盐水中缓慢腹腔注射,不超过CBV大鼠的1/10;4) MP + Noopept治疗EAE动物,剂量为10 mg/kg;5)用MP +胞胆碱(Ceraxon, Ferrer international s.a., Spain) D003U1系列,500 mg/kg灌胃治疗EAE动物。采用80x80x35 cm自建竞技场“开场”法研究大鼠脑电发射整合功能。记忆研究使用LE760 (AgnTho's,瑞典)径向迷宫进行。使用彩色摄像机SSC-DC378P (Sony, Japan)进行捕获和图像记录。使用Smartv 3.0软件(Harvard Apparatus, USA)进行视频文件分析。通过对多发性硬化症实验模型的研究发现,含有n-苯乙酰基-l-前酰甘氨酸乙酯的鼻凝胶具有正调节活性,抗抑郁和抗焦虑作用,增加中枢神经系统的总活性。结果表明,诺普鼻内凝胶具有高度的神经保护和益智活性。就减少工作记忆错误次数的影响程度而言,诺普凝胶明显超过了甲基强的松龙单药治疗以及甲基强的松龙和citicoline联合治疗。进一步研究该鼻凝胶对实验性多发性硬化症动物感觉运动皮质神经元形态功能指标的影响,以及对动物脑内HSP70含量的影响,是有希望的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neuroprotective properties of n-phenylacetyl-l-prolylglycine ethyl ester nasal gel in an experimental model of multiple sclerosis equivalent
The purpose of this research is to study the specific activity of our developed nasal dosage form with n-phenylacetyl-l-prolylglycine ethyl ester. The experiments were performed on 260 white outbred rats weighing 190-220 g. Experimental allergic encephalomyelitis (EAE) was induced by a single subcutaneous inoculation of an encephalitogenic mixture (EHM) in Complete Freund's Adjuvant (CFA) based on 100 mg of homologous spinal cord homogenate; 0.2 ml of CFA (the content of killed mycobacteria 5 mg/ml) and 0.2 ml of physiological saline per animal. There were five groups of animals in the study: 1) intact; 2) control - untreated with EAE, received saline solution; 3) animals with EAE that received basic treatment - methylprednisolone (MP), 3.4 mg/kg, intraperitoneally slowly in saline no more than 1/10 of the CBV rat; 4) animals with EAE treated with MP + Noopept, at a dose of 10 mg/kg; 5) animals with EAE treated with MP + Citicoline (Ceraxon, Ferrer Internacional S.A., Spain) D003U1 series, 500 mg/kg, intragastrically. The in­tegrative functions of rats’ brain with EAE were studied using the “Open Field” method with an arena of own production with dimensions 80x80x35 cm. The study of memory was carried out using the radial labyrinth LE760 (AgnTho's, Sweden). Capture and image recording was carried out using a color video camera SSC-DC378P (Sony, Japan). Video file analysis was performed using Smartv 3.0 software (Harvard Apparatus, USA). As a result of the stu­dies on experimental model of multiple sclerosis with a nasal gel containing ethyl ester of n-phenylacetyl-l-pro­lylglycine revealed the presence of normotimic activity, antidepressant and anxiolytic effects, an increase in the total activity of the central nervous system. The results obtained indicate a high neuroprotective and nootropic activity of the Noopept intranasal gel. By the degree of influence on reducing the number of errors in working memory, the Noopept gel sig­nificantly exceeds monotherapy with methylprednisolone and combination therapy with methylprednisolone and citi­coline. A further study of the effect of the developed nasal gel on the morphofunctional indices of sensorimotor cortical neurons under experimental multiple sclerosis, as well as on the content of HSP70 in the animal brain, is promising.
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