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

Effect of levodopa and clioquinol on antioxidant capacity in Parkinson's disease rhesus monkeys

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。

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.