牵正散提取物对帕金森病模型小鼠震颤、运动障碍、黑质神经元超微结构的影响

Effect of Qianzheng San Extract on Parkinsonian Tremor,Motor Dysfunction and Ultrastructure of DAnergic Neurons in Mice

目的:建立3种帕金森病小鼠模型,观察牵正散提取物对小鼠行为学影响,初步探讨其作用机制。方法:1昆明小鼠随机分组,设立模型组,牵正散低、高剂量组(1.7,5.0 g·kg-1),阳性药组(盐酸苯海索,3.35 mg·kg-1)。各治疗组小鼠连续ig给药4 d。末次给药后1 h,各组ip给予氢溴酸槟榔碱(25 mg·kg-1)或氧化震颤素(0.15 mg·kg-1)。记录各组小鼠震颤潜伏期和震颤持续时间。2C57BL/6小鼠随机分组,设立正常组,模型组,牵正散低、高剂量组剂量组(1.7,5.0 g·kg-1),阳性药组(美多芭,50 mg·kg-1)。除正常组,各组小鼠ip给予1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP,30 mg·kg-1),连续5 d。第6天开始治疗组ig给予牵正散提取物和美多芭,连续7 d,末次给药后检测小鼠行为学变化,电镜观察黑质神经元结构变化。结果:1小鼠ip槟榔碱或氧化震颤素后出现明显震颤,与模型组比较,牵正散提取物高剂量组震颤潜伏期显著延长(P<0.05),低、高剂量组震颤持续时间均显著缩短(P<0.01)。2与模型组比较,小鼠ip MPTP后出现明显运动障碍,黑质神经元超微结构明显损伤,经牵正散提取物处理后,小鼠自主活动次数增加、转棒潜伏期延长、爬杆时间缩短(P<0.05),黑质神经元线粒体等结构损伤程度减轻。结论:牵正散提取物显著抑制帕金森病模型小鼠震颤、改善运动障碍,其作用机制可能与减轻线粒体损伤、保护神经元有关。

Objective： To establish three types of parkinsonian mice models,observe the effect of Qianzheng San extract on mice behavior and explore possible mechanisms of its actions. Method： 1The Kunming mice were randomly divided into four groups： model group,Qianzheng San low dose group and high dose group（ 1. 7,5. 0 g·kg- 1）,positive drug group（ benzhexol hydrochloride,3. 35 mg·kg- 1）. The mice in the treatment groups received the corresponding medicines by intragastric administration for 4 days. 1 hour after the last administration,all mice were injected with arecoline hydrobromide（ 25 mg·kg- 1） or oxotremorine（ 0. 15 mg·kg- 1）. The incubation period and duration time of tremor were recorded. 2C57BL/6 mice were randomly divided into five groups： normal group,model group,Qianzheng San low dose group and high dose group（ 1. 7,5. 0 g·kg- 1）,positive drug group（ madopar,50 mg·kg- 1）. All mice except normal group were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropy-ridine（ MPTP,30 mg·kg- 1） for 5 consecutive days. From 6thday,the mice in treatment group received Qianzheng San extract or madopar by intragastric administration for 7 days. After the last treatment,behavior changes of the mice were detected and ultrastructure changes of substantia nigra neurons were observed by electron microscope. Result： 1After injection of arecoline hydrobromide or oxotremorine,the mice exhibited obvious tremor. Compared with the model group, Qianzheng San extract high-dose group significantly prolonged the incubation period of tremor（ P〈0. 05）,and Qianzheng San low dose group and high dose group significantly shortened the duration time of tremor（ P〈0. 01）. 2Compared with the model group,the MPTP-treated mice displayed a significant decrease in spontaneous motor activity and ultrastructure of substantia nigra neuron was obviously damaged. However,Qianzheng San extract treatment significantly increased autonomic activities,prolonged incubation period and shortened the pole-climbing time（ P〈0. 05）,and reduced the damage of ultrastructure of substantia nigra neurons. Conclusion： Qianzheng San extract could effectively suppress tremor and improve motor dysfunction in PD mice models, whose mechanism may be associated with reducing mitochondrial damages and protecting neurons.