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孟鲁司特在帕金森病实验模型中的作用。

Effect of montelukast in experimental model of Parkinson's disease.

作者信息

Nagarajan Vetrivel Babu, Marathe Padmaja Anil

机构信息

Seth GS Medical College, KEM Hospital, Mumbai, India.

出版信息

Neurosci Lett. 2018 Aug 24;682:100-105. doi: 10.1016/j.neulet.2018.05.052. Epub 2018 Jun 6.

Abstract

Despite the availability of many drugs offering symptomatic relief in Parkinson's disease, there are no drugs available offering neuroprotective effect. Hence, it was decided to evaluate the neuroprotective effect of montelukast, an anti-inflammatory drug, in rotenone induced model of Parkinson's disease in rats. Forty eight male wistar rats were randomly divided into three groups. Group 1: Vehicle control, Group 2: Montelukast 5 mg/kg, Group 3: Montelukast 10 mg/kg. All the groups received rotenone 2.5 mg/kg intraperitoneally for 10 days as a disease inducing agent. The study drug montelukast was administered to respective groups orally from day 11 to day 24. On day 25, 24 h after 14 days of study drug administration, the rats were subjected to open field test, rota rod test and catalepsy test. Brain samples of rats from each group were collected for Malondialdehyde(MDA), Glutathione(GSH) and TNFα analysis. In the open field test both the doses of montelukast showed significant increase in the locomotor activity and also decreased the immobility time compared to vehicle (p < 0.05). In rotarod test, montelukast 5 mg/kg and 10 mg/kg showed significant increase in the time to fall, compared to vehicle (p < 0.05). In catalepsy test, both doses of montelukast significantly decreased the retraction time compared to vehicle(p < 0.05). The brain MDA levels were decreased and GSH levels were found to be higher in the two montelukast groups compared to vehicle (p < 0.05). TNFα levels too were decreased significantly on montelukast administration. Montelukast showed potential neuroprotective effect by virtue of its anti-oxidant and anti-inflammatory actions.

摘要

尽管有许多药物可缓解帕金森病的症状,但目前尚无具有神经保护作用的药物。因此,研究人员决定评估抗炎症药物孟鲁司特对鱼藤酮诱导的大鼠帕金森病模型的神经保护作用。48只雄性Wistar大鼠被随机分为三组。第1组:溶剂对照组;第2组:孟鲁司特5mg/kg组;第3组:孟鲁司特10mg/kg组。所有组均腹腔注射2.5mg/kg鱼藤酮,持续10天作为疾病诱导剂。从第11天至第24天,将研究药物孟鲁司特口服给予相应组。在第25天,即给予研究药物14天后的24小时,对大鼠进行旷场试验、转棒试验和僵住症试验。收集每组大鼠的脑样本进行丙二醛(MDA)、谷胱甘肽(GSH)和肿瘤坏死因子α(TNFα)分析。在旷场试验中,与溶剂对照组相比,孟鲁司特的两个剂量组均显示出自发性活动显著增加,不动时间减少(p<0.05)。在转棒试验中,与溶剂对照组相比,孟鲁司特5mg/kg和10mg/kg组的跌落时间显著增加(p<0.05)。在僵住症试验中,与溶剂对照组相比,孟鲁司特的两个剂量组均显著缩短了伸展时间(p<0.05)。与溶剂对照组相比,两个孟鲁司特组的脑MDA水平降低,GSH水平升高(p<0.05)。给予孟鲁司特后,TNFα水平也显著降低。孟鲁司特凭借其抗氧化和抗炎作用显示出潜在的神经保护作用。

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