卡介苗对鱼藤酮诱导的帕金森病的作用:神经炎症和神经递质的作用。

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2023-12-02 DOI:10.1111/fcp.12968

Narhari Gangaram Yedke, Divya Soni, Puneet Kumar

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引用次数: 0

摘要

背景:帕金森病(PD)是一种锥体外系运动障碍，与大脑黑质纹状体区域多巴胺能神经元活力受损引起的运动障碍相关。目前的药物只能提供症状管理;到目前为止，还没有永久性的治疗方法。为了弥补这一空白，研究人员对基于抗原的治疗越来越感兴趣，卡介苗(BCG)是一种具有高安全性的疫苗，通过刺激中枢神经系统中的免疫反应性t细胞，减少包括白细胞介素(IL)-1β和肿瘤坏死因子(TNF-α)在内的促炎细胞因子的表达来产生神经保护作用。先前的一项研究报告称，卡介苗对几种神经退行性疾病(如阿尔茨海默病)具有神经保护作用。目的:探讨卡介苗对鱼藤酮模型帕金森病的神经保护作用。方法:大鼠连续注射鱼藤酮(1.5 mg/kg, s.c)和卡介苗(2 × 107 cfu, i.p)单剂量，分别于第21、28天进行行为学评价。第29天处死大鼠，分离脑进行生化和神经化学评价。结果:卡介苗可显著恢复鱼藤酮诱导的运动障碍(开场试验、窄梁行走和轮虫行走)、纹状体生化水平(GSH、SOD、过氧化氢酶、MDA和亚硝酸盐)、神经递质(多巴胺、5-羟基色胺、去甲肾上腺素、3,4-二羟基苯乙酸、血香草酸和5-羟基吲哚乙酸)和炎症因子(IL-1β和TNF-α)水平。它还通过减少纹状体中的嗜酸性损伤来防止组织病理学变化。结论:卡介苗通过抗氧化和抗炎作用发挥神经保护作用。因此，在未来，它可以作为一种神经保护剂用于其他神经系统疾病，包括PD。

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Effect of Bacille-Calmette-Guerin vaccine against rotenone-induced Parkinson's disease: Role of neuroinflammation and neurotransmitters

Background

Parkinson's disease (PD) is an extrapyramidal movement disorder associated with a hypokinetic condition generated by impairment in dopaminergic neuronal viability in the nigrostriatal region of the brain. Current medications can only provide symptomatic management; to date, no permanent cure is available. To compensate for this lacuna, researchers are gaining interest in antigen-based therapy, and Bacille-Calmette-Guerin (BCG) is one of the vaccines with a high safety margin that acts by stimulating immunoreactive T-cells in the CNS and reducing expression of pro-inflammatory cytokines including interleukin (IL)-1β and tumor necrotic factor (TNF-α) to produce neuroprotection. A previous study reported that BCG exerts a neuroprotective effect against several neurodegenerative disorders, such as Alzheimer's disease.

Objective

The objective of this study is to explore the neuroprotective effect of the BCG vaccine against the rotenone model of PD.

Methods

Rotenone (1.5 mg/kg, s.c) for 28 days, and BCG vaccine (2 × 10⁷ cfu, i.p) single dose was injected to rats, and behavioral assessments were performed on the 21st and 28th day. On the 29th day, rats were sacrificed, and brains were isolated for biochemical and neurochemical estimation.

Results

BCG vaccine significantly restored rotenone-induced motor deficits (open field test, narrow beam walk, and rotarod), biochemical levels (GSH, SOD, catalase, MDA, and nitrite), neurotransmitters (dopamine, 5-hydroxy tryptamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, hemovanillic acid, and 5-hydroxy indoleacetic acid), and levels of inflammatory cytokines (IL-1β and TNF-α) in the striatum. It also prevents histopathological changes by reducing eosinophilic lesions in the striatum.

Conclusion

From the results, we conclude that BCG vaccine showed neuroprotection through antioxidant and anti-inflammatory effect. Thus, in the future, it can be used as a neuroprotective agent for other neurological disorders, including PD.

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.