isatin和afobazole对鱼藤酮诱导的帕金森病大鼠的神经保护作用伴随着Triton X-100可溶性α-突触核蛋白的脑水平升高。

Q3 Biochemistry, Genetics and Molecular Biology Biomeditsinskaya khimiya Pub Date : 2023-11-01 DOI:10.18097/PBMC20236905290
O A Buneeva, I G Kapitsa, V G Zgoda, A E Medvedev
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引用次数: 0

摘要

研究了内源性神经保护剂isatin和药理学药物afobazole(表现出神经保护特性)对实验性鱼藤酮帕金森病大鼠行为反应和脑蛋白质组定量变化的影响。在开阔场地试验(水平运动)和旋转杆试验中,单剂量的isatin(在7天鱼藤酮给药疗程的最后一天皮下注射100mg/kg)改善了鱼藤酮诱导的帕金森病大鼠的运动活性。阿福唑(10 mg/kg腹膜内,在鱼藤酮给药的7天过程中每天)减少了僵硬和姿势不稳定的表现。使用最后一次施用鱼藤酮和神经保护剂后第二天获得的大脑样本进行的蛋白质组学分析显示,患有鱼藤酮帕金森病的大鼠大脑中存在类似的定量变化。检测到65种蛋白质的相对含量的增加和21种蛋白质相对含量的减少。最明显的变化——α-突触核蛋白含量增加了近90倍——是在用isatin治疗的大鼠大脑中发现的。在用“鱼藤酮+艾沙汀”和“鱼藤酮+阿福唑”治疗的实验组动物中,该蛋白质在大脑中的相对含量的增加几乎是对照值的60和50倍。考虑到关于α-突触核蛋白生理作用的已知数据,在对患有鱼藤酮-帕金森病的动物施用神经保护剂后,大脑中这种蛋白质含量的增加可能代表一种补偿反应,至少在该疾病的早期和治疗开始时是如此。
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Neuroprotective effects of isatin and afobazole in rats with rotenone-induced Parkinsonism are accompanied by increased brain levels of Triton X-100 soluble alpha-synuclein.

Effects of the endogenous neuroprotector isatin and the pharmacological drug afobazole (exhibiting neuroprotective properties) on behavioral reactions and quantitative changes in the brain proteomic profile have been investigated in rats with experimental rotenone Parkinsonism. A single dose of isatin (100 mg/kg subcutaneously on the last day of a 7-day course of rotenone administration) improved the motor activity of rats with rotenone-induced Parkinsonism in the open field test (horizontal movements) and the rotating rod test. Afobazole (10 mg/kg intraperitoneally, daily during the 7-day course of rotenone administration) reduced the manifestations of rigidity and postural instability. Proteomic analysis, performed using brain samples obtained the day after the last administration of rotenone and neuroprotectors, revealed similar quantitative changes in the brain of rats with rotenone Parkinsonism. An increase in the relative content of 65 proteins and a decrease in the relative content of 21 proteins were detected. The most pronounced changes - an almost ninety-fold increase in the alpha-synuclein content - were found in the brains of rats treated with isatin. In animals of the experimental groups treated with "Rotenone + Isatin", as well as "Rotenone + Afobazole", the increase in the relative content of this protein in the brain was almost 60 and 50 times higher than the control values. Taking into consideration the known data on the physiological role of alpha-synuclein, an increase in the content of this protein in the brain upon administration of neuroprotectors to animals with rotenone Parkinsonism may represent a compensatory reaction, at least in the early stages of this disease and the beginning of its treatment.

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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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