摘要
目的 研究左旋多巴 (L dopa)对帕金森病 (PD)模型大鼠异常行为、黑质抗氧化系统、线粒体呼吸链功能和神经递质代谢的影响及其机制。方法 应用 6 羟基多巴胺 (6 OHDA)立体定向注射制作PD大鼠模型 ,给PD大鼠L dopa 2 5mg/ (kg·d)灌胃 ,共 4 5d。给药前后分别进行行为学测试 ,给药后测定黑质区谷胱甘肽过氧化物酶 (GSH Px)、丙二醛 (MDA)、活性氧 (ROS)及线粒体呼吸链酶复合体Ⅰ水平 ,测定尾状核头部多巴胺 (DA)、高香草酸 (HVA)、单胺氧化酶 B(MAO B)的水平。结果 (1)L dopa组大鼠旋转速度给药前为(13.1± 1.5 )r/min ,给药后为 (7.2± 1.6 )r/min,给药前后比较差异有显著性 (P <0 .0 1) ;(2 )L dopa组GSH Px活性、呼吸链酶复合体Ⅰ水平降低 ,MDA含量、ROS活性升高 ,与对照组比较差异均有显著性 (均P <0 .0 1) ;(3)L dopa组MAO B活性、DA、HVA含量及DA/HVA比值与对照组比较均显著升高 (P <0 .0 5～ 0 .0 1)。结论L dopa能有效改善PD大鼠的旋转行为 ,但可加重黑质区氧化应激损伤 ,抑制线粒体呼吸链酶活性。
Objective To study the effects of Levodopa on the abnormal behavior, nigral antioxidation system, mitochondrial respiration-chain function, neurotransmitter metabolism of Parkinson's disease (PD) model rat and its mechanism.Methods The rat models of PD were established through stereotaxic microinjection of 6-hydroxydopamine (6-OHDA). The rats in levodopa group were given levodopa 25 mg/(kg·d) through intragastric administration for 45 days. All the rats’behavior was tested before and after giving medicine. The activity of glutathione peroxidase(GSH-Px) and ROS, contents of malondialdedyde(MDA) and mitochondrial respiratory chain enzyme complex Ⅰ in nigra and the contents of dopamine(DA), homovanillic acid(HVA) and activity of monoamine oxidase-B(MAO-B) in caudate nucleus were assayed after treatment.Results (1) Compared with before treatment, the rotation rate after treatment decreased obviously( P<0.01). (2) In levodopa group, GSH-Px activity and mitochondrial respiratory chain enzyme complex Ⅰ level reduced, ROS activity and MDA content increased. The differences were significant compared with the controls (all P<0.01). (3) Compared with control group, MAO-B activity in levodopa group increased, DA, HVA contents and DA/HVA ratio increased obviously( P<0.05 or P<0.01).Conclusion Levodopa may obviously decrease rotation behavior of PD model rats but aggravate oxidative stress of nigra, restrain the activity of mitochondrial respiratory chain.
出处
《临床神经病学杂志》
CAS
2004年第5期354-356,共3页
Journal of Clinical Neurology
关键词
帕金森病
左旋多巴
氧化应激
线粒体呼吸链
parkinson's disease
levodopa
oxidative stress
mitochondrial respiratory chain
