龟芍平颤方联合多巴丝肼片对帕金森病小鼠行为学和神经递质的影响  

Effects of Guishaopingchan compound combined with levodopa and benserazide hydrochloride tablets on behavior and neurotransmitters of Parkinson’s disease mouse

作　　者：房泽海[1] 董含秋 陈亮 吴倩 张叶[1] 张炅璐 刘红杰 FANG Ze-hai;DONG Han-qiu;CHEN Liang;WU Qian;ZHANG Ye;ZHANG Jiong-lu;LIU Hong-jie(Department of Pharmacy,Zibo Vocational Institute,Zibo SHANGDONG 255314,China;School of Traditional Chinese Medicine,Ji-nan University,Guangzhou GUANGDONG 510632,China)

机构地区：[1]淄博职业学院药学系,山东淄博255314 [2]暨南大学中医学院,广东广州510632

出　　处：《中国新药与临床杂志》2020年第7期429-434,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：山东省重点研发计划项目(2018GSF118149);广东省中医药局科研项目(20161064)。

摘　　要：目的观察龟芍平颤方联合小剂量多巴丝肼片对帕金森病(PD)小鼠行为学和纹状体多巴胺(DA)及其代谢产物的影响。方法将雄性C57BL/6小鼠随机分为对照组,模型组,多巴丝肼片10、50 mg·kg^-1组,龟芍平颤方组,合方(龟芍平颤方+多巴丝肼片10 mg·kg^-1)组。各组按相应剂量灌胃给药,连续14 d。首次给药30 min后,除对照组外,其余组按体重25 mg·kg^-1腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP),连续7 d,制备PD小鼠模型。给药当日起记录小鼠行为学改变,共观察14 d。采用爬杆、悬挂和自主活动实验观察小鼠行为学变化,HE染色法观察小鼠中脑黑质形态学变化,高效液相色谱串联质谱(HPLC/MS)法测定小鼠纹状体DA及其代谢产物含量。结果与对照组比较,模型组爬杆评分增加,悬挂评分和自主活动评分显著降低(P <0.01),DA、高香草酸(HVA)、3,4-二羟基苯乙酸(DOPAC)含量显著减少(P <0.01)。与模型组比较,从给药第7日起合方组爬杆、悬挂、自主活动明显改善(P <0.05),且从第11日起,显著优于龟芍平颤方组和多巴丝肼片10、50 mg·kg^-1组(P <0.05);合方组DA、HVA、DOPAC含量显著高于模型组(P <0.01),且显著高于多巴丝肼片10 mg·kg^-1组和龟芍平颤方组(P <0.05)。结论龟芍平颤方联合小剂量多巴丝肼片具有协同作用,可改善PD模型小鼠的行为学症状、调节小鼠DA及其代谢产物含量。AIM To observe the effects of Guishaopingchan compound combined with low-dose levodopa and benserazide hydrochloride tablets(LBH) on behavior and dopamine(DA) and its metabolites of the mouse model of Parkinson’s disease(PD). METHODS C57 BL/6 male mice were randomly divided into control group, model group, LBH 10 and 50 mg·kg^-1 groups, Guishaopingchan compound group and combine group(Guishaopingchan compound + LBH 10 mg·kg^-1).Each group was intragastrically administered at the corresponding dose for 14 days. And 30 minutes after the first administration, PD mice models were prepared by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) 25 mg·kg^-1 for 7 days, except for the control group. From the day of administration, the behavioral changes of mice were observed and recorded for 14 days. The behavioral changes of mice were observed by climbing experiment, hanging test and autonomic activity counting. The morphological changes of the substantia nigra in mice were observed by HE staining. The levels of dopamine(DA) and its metabolites in mice striatum were determined by HPLC/MS. RESULTS Compared with the control group, the climbing scores were increased, suspension scores and autonomous activity scores were decreased in the model group(P < 0.01). And the contents of DA, homovanillic acid(HVA) and dihydroxy-phenyl acetic acid(DOPAC) were significantly reduced(P < 0.01). Compared with the model group, the climbing, suspension and autonomous activity scores in the combine group were significantly improved after 7 days of administration(P < 0.05), and the scores in the combine group were significantly better than the Guishaopingchan compound group and LBH 10, 50 mg·kg^-1 groups after 11 days(P < 0.05). DA, HVA and DOPAC contents of the combine group were significantly higher than the model group and the LBH 10 mg·kg^-1 and Guishaopingchan compound group(P < 0.05). CONCLUSION Guishaopingchan compound combined with low-dose LBH has synergistic effect which can improve the behavi

关 键 词：帕金森病 龟芍平颤方 多巴丝肼片 多巴胺 高香草酸 小鼠 

分 类 号：R285.5[医药卫生—中药学] R971[医药卫生—中医学]