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辅酶 Q 与辅酶 Q/左旋多巴-卡比多巴联合对小鼠帕金森病作用的研究

An Investigation of the Anti-Parkinsonism Potential of Co-enzyme Q and Co-enzyme Q /Levodopa-carbidopa Combination in Mice.

机构信息

Department of Pharmacology, Behavioural Neuroscience/Neuropharmacology Unit, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria.

Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria.

出版信息

Curr Aging Sci. 2021;14(1):62-75. doi: 10.2174/1874609812666191023153724.

DOI:10.2174/1874609812666191023153724
PMID:31702498
Abstract

Despite decades of research, neurodegenerative disorders like Parkinson's disease remain a leading cause of disability worldwide, due to the insufficient reduction of disease burden by available medications. Recently, the benefits of dietary supplements like co-enzyme Q in neurodegenerative diseases have been reported. ; Aim: The protective effects of supplemental co-enzyme Q (CQ) and possible additive benefits of CQ /Levodopa-Carbidopa (LD) in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice were investigated. ; Methods: Male mice were assigned to ten groups of 30 mice each. Groups included: Vehicle control (fed Standard Diet (SD), and given intraperitoneal {ip} plus oral saline), LD group (fed SD, and given ip saline plus oral LD), two groups fed CQ-supplemented diet (at 60 and 120 mg/kg of feed), and given ip plus oral saline, CPZ group (fed SD, and given ip CPZ plus oral saline), CPZ/LD group (fed SD, and given ip CPZ plus oral LD), two groups fed CQ-supplemented diet (at 60 and 120 mg/kg of feed) and given ip CPZ plus oral saline, and another two groups fed CQ-supplemented diet (at 60 and 120 mg/kg of feed) and given ip CPZ plus oral LD. The total duration of study was 21 days, and treatments were administered daily. Bodyweight and food intake were measured weekly, while neurobehavioural and biochemical tests were assessed at the end of the experimental period. ; Results: CQ-supplementation was protective against CPZ-induced parkinsonism-like changes including, reduction in mortality, the reversal of retardation of open-field behaviours and reduction of catalepsy, increase in dopamine levels and decreased oxidative stress. CQ also showed significant improvements in these parameters when co-administered with LD. CQ (in groups administered CPZ/CQ 60) showed greater benefit over LD on anxiety-related behaviours and also had additive benefits on working-memory. ; Conclusion: Dietary CQ-supplementation was associated with demonstrable benefits in CPZinduced Parkinsonism-like changes in mice.

摘要

尽管经过了几十年的研究,但由于现有药物对疾病负担的减轻程度不足,神经退行性疾病(如帕金森病)仍是全球致残的主要原因。最近,已有研究报道称膳食补充剂辅酶 Q 对神经退行性疾病有益。目的:研究补充辅酶 Q(CQ)对氯丙嗪(CPZ)诱导的帕金森样变化小鼠的保护作用,以及 CQ/左旋多巴-卡比多巴(LD)的可能附加益处。方法:雄性小鼠分为 10 组,每组 30 只。分组如下:对照组(给予标准饮食(SD),腹腔内注射生理盐水和口服生理盐水)、LD 组(给予 SD,腹腔内注射生理盐水和口服 LD)、两组 CQ 补充饮食组(饲料中添加 60 和 120mg/kg 的 CQ),腹腔内注射生理盐水加口服生理盐水、CPZ 组(给予 SD,腹腔内注射 CPZ 加口服生理盐水)、CPZ/LD 组(给予 SD,腹腔内注射 CPZ 加口服 LD)、两组 CQ 补充饮食组(饲料中添加 60 和 120mg/kg 的 CQ),腹腔内注射 CPZ 加口服生理盐水,以及两组 CQ 补充饮食组(饲料中添加 60 和 120mg/kg 的 CQ),腹腔内注射 CPZ 加口服 LD。研究总时长为 21 天,每天进行治疗。每周测量体重和食物摄入量,在实验结束时进行神经行为学和生化测试。结果:CQ 补充剂可预防 CPZ 诱导的帕金森样变化,包括降低死亡率、逆转旷场行为迟缓以及减少僵直、增加多巴胺水平和降低氧化应激。当与 LD 一起给药时,CQ 也显示出对这些参数的显著改善。CQ(在接受 CPZ/CQ 60 的组中)在焦虑相关行为方面显示出比 LD 更大的益处,并且在工作记忆方面也具有附加益处。结论:膳食 CQ 补充与 CPZ 诱导的帕金森样变化小鼠中可观察到的益处有关。

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