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浙江大学学报（农业与生命科学版）
浙江大学学报(农业与生命科学版)  2017, Vol. 43 Issue (3): 371-376    DOI: 10.3785/j.issn.1008-9209.2016.05.251
动物科学与动物医学     
左旋多巴和氯碘羟喹治疗对帕金森病猕猴血清抗氧化能力的影响
李立科1，史良琴1，刘衡1，罗启慧1,2，黄超1，刘文涛1,2，陈晓林1，陈正礼1,2*
1.四川农业大学动物医学院，实验动物疾病模型研究室，成都 611130；2.四川农业大学实验动物工程技术中心，四川 雅安 625014
Effect of levodopa and clioquinol on antioxidant capacity in Parkinson’s disease rhesus monkeys
LI Like1, SHI Liangqin1, LIU Heng1, LUO Qihui1,2, HUANG Chao1, LIU Wentao1,2, CHEN Xiaolin1, CHEN Zhengli1,2*
(1. Laboratory of Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; 2. Engineering and Technology Center for Laboratory Animals, Sichuan Agricultural University, Ya’an 625014, Sichuan, China)
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摘要： 探讨左旋多巴和氯碘羟喹对帕金森病（Parkinson’s disease，PD）猕猴的治疗效果及血液抗氧化指标的影响，以期为PD药物治疗判定提供参考依据。利用1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP）小剂量肌肉注射建立慢性PD猕猴模型，将8只PD猕猴随机分为左旋多巴组（3只）、氯碘羟喹组（3只）和对照组（2只），连续4周分别经口给予左旋多巴+卡比多巴15 mg/kg、氯碘羟喹15 mg/kg和等量的生理盐水，每天观察记录并运用PD 评定量表进行行为评分；测定治疗前后PD 猕猴血清超氧化物歧化酶（superoxide dismutase, SOD）、丙二醛（malondialdehyde, MDA）、谷胱甘肽（glutathione, GSH）、谷胱甘肽过氧化物酶（glutathione peroxidase, GPX）以及谷胱甘肽硫转移酶（glutathione S-transferase, GST）的水平。结果发现：与同组治疗前相比，左旋多巴组和氯碘羟喹组PD猕猴行为评分下降，差异有统计学意义，而对照组无明显差异；左旋多巴组和氯碘羟喹组的SOD、GPX和GST活性和GSH含量均增加，MDA含量均降低，其中，左旋多巴组上述各指标的差异均有统计学意义（P＜0.05），氯碘羟喹组的GST活性和GSH含量差异也具有统计学意义（P＜0.05）。与仅注射生理盐水的对照组相比，左旋多巴组的SOD和GST活性显著增加，差异有高度统计学意义（P＜0.01），GPX活性和MDA含量降低（P＜0.05）；氯碘羟喹组的SOD活性和GSH含量显著增加，差异有统计学意义（P＜0.05），GPX活性显著降低（P＜0.01），其他各生化指标间差异无统计学意义。综上表明，不同药物治疗通过提高PD猕猴血液中抗氧化酶的活性，降低脂质过氧化物的含量，增强机体的抗氧化能力，促进了猕猴临床行为的恢复，从而对治疗起到了积极作用。
Abstract: Parkinson’s disease (PD), characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta of the brain，is the second most common neurodegenerative disease. It includes the major motor symptoms of akinesia, rigidity and tremor. Main mechanisms of the neuronal degeneration of PD include free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes,  genetic factors, environmental impact factors, toxic action of nitric oxide, and apoptosis, all of which may interact with and amplify each other in a vicious cycle of toxicity, leading to neuronal dysfunction, atrophy, and finally cell death.
Eight healthy young rhesus monkeys were respectively daily injected a small dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by intramuscular injection, then divided into a levodopa group (three rhesus monkeys), a clioquinol group (three rhesus monkeys) and a control group (two rhesus monkeys) randomly, and given 15 mg/kg levodopa + carbidopa,15 mg/kg clioquinol and equal physiological saline by oral for 4 weeks respectively. The behavioral manifestations of all monkeys were evaluated, and their serum biochemical indices were measured before and after different drug treatments, including superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione S- transferase (GST), glutathione (GSH) and malondialdehyde (MDA).
With the continued injection of MPTP, the monkeys reached a state of stable parkinsonism, which was first obtained on the 62 days of treatment. Since then, no significant variation was observed. In addition, vocalization reduction was the first symptom, but it was indistinct; furthermore, we found that the monkeys became increasingly bradykinetic, and finally presented with tremors, which were stronger and earlier at the arms than at the legs. Other early phenotypes and long-lasting symptoms included a decrease in home cage activity and arm movement, and an increase of muscular rigidity and freeze. The behavior scores of the levodopa group and clioquinol group decreased after the treatment, and the difference was statistically significant, but the control group showed no significant differences. The activities of SOD, GPX, GST and the GSH content were all increased, while MDA concentration decreased in the levodopa group and clioquinol group; the above indexes in the levodopa group had statistical significance (P＜0.05), as well as the levels of GST and GSH in the clioquinol group (P＜0.05). Compared with the control group, the activities of SOD and GST increased significantly (P＜0.01), while the GPX activity and the MDA concentration decreased significantly (P＜0.05) in the levodopa group; the SOD activity and the GSH content increased significantly (P＜0.05), but the GPX activity decreased significantly (P＜0.01) in the clioquinol group. 
The above results show that levodopa and clioquinol can increase the blood antioxidant enzyme activity and decrease the lipid peroxide content, and then enhance the body’s antioxidant capacity and promote the recovery of clinical behavior, thus playing a positive role in PD monkeys.
收稿日期: 2016-05-25 出版日期: 2016-08-02
CLC:  Q 95-331  
基金资助: 国家科技支撑计划（2014BAI03B01）；国家重大科学仪器设备开发专项（2013YQ49085906）
通讯作者: 陈正礼(http://orcid.org/0000-0002-9850-528X)     E-mail: chzhli75@163.com
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引用本文:

李立科，史良琴，刘衡，罗启慧，黄超，刘文涛，陈晓林，陈正礼. 左旋多巴和氯碘羟喹治疗对帕金森病猕猴血清抗氧化能力的影响[J]. 浙江大学学报(农业与生命科学版), 2017, 43(3): 371-376.

LI Like, SHI Liangqin, LIU Heng, LUO Qihui, HUANG Chao, LIU Wentao, CHEN Xiaolin, CHEN Zhengli. Effect of levodopa and clioquinol on antioxidant capacity in Parkinson’s disease rhesus monkeys. Journal of Zhejiang University (Agriculture and Life Sciences), 2017, 43(3): 371-376.

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http://www.zjujournals.com/agr/CN/10.3785/j.issn.1008-9209.2016.05.251    或    http://www.zjujournals.com/agr/CN/Y2017/V43/I3/371

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