《中国康复理论与实践》

《中国康复理论与实践》 ›› 2002, Vol. 8 ›› Issue (09): 513-515.

• 专题研究 •    下一篇

中药复方参乌胶囊对亨廷顿病大鼠模型运动功能及脑内单胺类神经递质含量的影响

张如意; 张兰; 李林; 王辉; 叶翠飞   

  1. 首都医科大学宣武医院药理研究室,北京市脑老化重点实验室 北京市 100053
  • 收稿日期:2002-07-16 出版日期:2002-09-25 发布日期:2002-09-25

Effects of Shen-wu Capsule on motor function and content of dopamine in striatum in Huntington model rats

ZHANG Ru-yi,ZHANG Lan,LI Lin,et al   

  1. Department of Pharmacology, Beijing Key Laboratoryfor Brain Aging,Xuan-wu Hospital of Capital University of Medical Sciences,100053 Beijing,China
  • Received:2002-07-16 Published:2002-09-25 Online:2002-09-25

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被引次数

5

摘要： 目的探讨线粒体缺陷在亨廷顿病(HD)中的作用并观察中药复方参乌胶囊的干预作用。方法雄性SD大鼠分为6组,每组10只。模型组:线粒体呼吸链复合体Ⅱ/Ⅲ抑制剂3硝基丙酸(3 NPA)20mg/kg隔日腹腔注射1次,共20天;参乌胶囊用药组根据剂量分为小剂量组、中剂量组、大剂量组:从造模前5天开始给予参乌胶囊0.45g/kg、0.9g/kg、18g/kg,每日1次,共2 5天;氟哌啶醇组:造模的同时给予氟哌啶醇,起始剂量为10μg/100g体重,以后隔日递增10μg/100g体重,至100μg/100g体重;正常对照组(9只),隔日腹腔注射与模型组等剂量的生理盐水,蒸馏水灌胃。旷场分析实验检测各组大鼠模型的中枢兴奋状态及空间认知能力,攀网实验检测动物肌力变化,高效液相色谱-电化学检测法分别测定各组动物纹状体中多巴胺(DA)、其代谢产物二羟基苯乙酸(DOPAC)及5羟色胺(5-HT)的含量。结果旷场分析实验中模型组大鼠较正常对照组理毛次数、站立次数、跨格次数分别减少74.69%,64.46%,53.0 6%,具有非常显著性差异(P<0.01),参乌胶囊用药组较模型组理毛次数增加了68%(P<0.01);攀网实验中,各组动物攀附时间无差异;模型组大鼠较正常对照组DA、DOPAC和5-HT的含量明显降低(P<0.01),而参乌胶囊用药组、氟哌啶醇组动物纹状体中上述递质及其代谢产物的含量都较模型组明显升高(P<0.01)。结论 腹腔注射3-NPA可以造成大鼠运动功能及脑纹体内单胺类神经递质的改变,而中药复方参乌胶囊对3-NPA动物模型的行为学及脑纹状体中单胺类神经递质含量具有明显的改善和提升作用。

关键词: 3-硝基丙酸, 亨廷顿病, 多巴胺, 纹状体, 中草药

Abstract: ObjectiveTo investigate the role of mitochondrial dysfunction in neurodegenerative diseases and the pharmacological effects of Shen-wu Capsule.MethodsSD rats were divided into 6 groups with 10 rats each:model group was developed by peritoneal injection of 3-nitropropionic acid(3-NPA) 20mg/kg, once every another day. Haloferidoli was used as the positive drug (given to positive control group from 10μg/100g/day to 100μg/100g/day, during modeling). Low dose of Shen-wu Capsule is 0.45g/kg; middle dose of Shen-wu Capsule is 0.9g/kg; high dose of Shen-wu Capsule is 1.8g/kg (once a day for 25days). The rats in normal control group were peritoneally injected with saline and were fed with water.The open field test was used to test the space recognition ability and excitability of CNS of rats. The climbing test was used to test strength of muscles.The content of dopamine(DA) and it's metabolite dihydroxyphenylacetic acid (DOPAC),5-HT in stratium of all groups were detected by high performance liquid chromatograph (HPLC-ECD).ResultsThe 3-NPA model rats showed decrease of activity, rigidity and stagger just like clinical patients with Huntington's diseases. In open field test all indexes of 3-NPA model rats are decreased (P<0.05), while Shen-wu Capsule low dose and high dose can improve all the indexes. There is no difference in strength of muscles among all groups. The content of DA,DOPAC and 5-hydroxytryptamine (5-HT) were distinctly decreased in 3-NPA model rats(P<0.01); rats in three groups of Shen-wu Capsule and positive drug control groups showed increased content of these neurotransmitter(P<0.01). Conclusions Rats injected with 3-NPA can mimic the abnormal behaviors and changes of neurotransmitter in stratium of Huntington's patients, Shen-wu Capsule can ameliorate the behavior of model animals and improve the content of DA,DOPAC and 5-HT in stratium.

Key words: 3-nitropropionic acid(3-NPA), Huntington's disease, dopamine, stratium, Chinese herbs