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诺司卡品对百草枯诱导的大鼠帕金森病保护作用的评估

Evaluation of the Protective Effects of Noscapine on Paraquat-Induced Parkinson's Disease in Rats.

作者信息

Bosak Fatemeh, Baradaran Rahimi Vafa, Sobhani Bashir, Dabbaghi Mohammad Mahdi, Soukhtanloo Mohammad, Zahedi Avval Farnaz, Askari Vahid Reza

机构信息

Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Mol Neurobiol. 2025 May 6. doi: 10.1007/s12035-025-05000-6.

Abstract

Parkinson's disease (PD) is a degenerative central nervous system disease pathologically attributed to dopaminergic neuron damage in the substantia nigra. Noscapine is a natural alkaloid with several benefits, including anti-inflammatory, neural protection, and anti-oxidant effects. Hence, the current study evaluated the protective effects of Noscapine against paraquat (PQ)-induced Parkinson's disease model in rats. Male Wistar rats were into six groups: sham and PQ-induced models treated with vehicle, vitamin-E (20 mg/kg/d), or Noscapine (6, 18, and 55 mg/kg/d) for four weeks. Meanwhile, the rats were assessed for weight and food consumption (FC) daily and PD-associated behavior changes using rotarod, bar, and parallel bar tests every week. The animals were ethically sacrificed at the end of the study, and biochemical, immunological, and histopathological markers were measured in the brain. As a result, the levels of weight, FC, parallel bar, and rotarod test (both speed and latency), number of neurons, total thiol content, and interleukin-10 (IL-10) were significantly reduced. In contrast, the levels of dark neurons, TNF-α, bar test, and malondialdehyde (MDA) were markedly increased in the PQ-vehicle group compared to the sham group (P < 0.001-0.5). In contrast, comedication with Noscapine significantly reversed the histological damages and improved deteriorated behavioral, biochemical, and immunological parameters in a dose-dependent manner compared to the PQ-vehicle group (0.001-0.05). Taken together, it was determined that using Noscapine has antiparkinsonian effects and improved behavioral tests, catalepsy, bradykinesia, and motor dysfunction and has a protective impact on the brain's neurons through its anti-oxidant and anti-inflammatory properties.

摘要

帕金森病(PD)是一种中枢神经系统退行性疾病,病理上归因于黑质中多巴胺能神经元的损伤。那可丁是一种天然生物碱,具有多种益处,包括抗炎、神经保护和抗氧化作用。因此,本研究评估了那可丁对百草枯(PQ)诱导的大鼠帕金森病模型的保护作用。将雄性Wistar大鼠分为六组:假手术组和PQ诱导模型组,分别用赋形剂、维生素E(20mg/kg/d)或那可丁(6、18和55mg/kg/d)处理四周。同时,每天评估大鼠的体重和食物消耗量(FC),每周使用转棒试验、平衡木试验和平行杠试验评估与PD相关的行为变化。在研究结束时对动物进行伦理处死,并测量大脑中的生化、免疫和组织病理学指标。结果,体重、FC、平行杠试验和转棒试验(速度和潜伏期)、神经元数量、总硫醇含量和白细胞介素-10(IL-10)水平显著降低。相比之下,与假手术组相比,PQ-赋形剂组中深色神经元、肿瘤坏死因子-α、平衡木试验和丙二醛(MDA)水平显著升高(P<0.001-0.5)。相反,与PQ-赋形剂组相比,那可丁联合用药显著逆转了组织学损伤,并以剂量依赖方式改善了恶化的行为、生化和免疫参数(0.001-0.05)。综上所述,确定使用那可丁具有抗帕金森病作用,改善了行为测试、僵住症、运动迟缓及运动功能障碍,并通过其抗氧化和抗炎特性对大脑神经元具有保护作用。

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