基于均匀设计的龟芍平颤方联合多巴丝肼片抗帕金森病剂量配比筛选与验证  

Screening and Verification on Doses of Guishaopingchan Compound Combined with Levodopa and Benserazide Hydrochloride Tablets by Uniform Design for Parkinson’s Disease

作　　者：刘红杰 张炅璐 董含秋 陈亮 何涛志 吴倩 房泽海[2] Liu Hongie;Zhang Jionglu;Dong Hanqiu;Chen Liang;He Taozhi;Wu Qian;Fang Zehai(School of Traditional Chinese Medicine,Jinan University,Guangzhou 510632;Department of Pharmacy,Zibo Vocational Institute,Zibo 255314)

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

出　　处：《中药药理与临床》2020年第1期163-168,共6页Pharmacology and Clinics of Chinese Materia Medica

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

摘　　要：目的:基于均匀设计法筛选龟芍平颤方联合多巴丝肼片抗帕金森病(PD)的剂量配比,并运用相同的动物模型验证其疗效。方法:在前期筛选出抗PD的龟芍平颤方(白芍、龟甲、天麻、川芎)联合多巴丝肼片的基础上,运用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导C57BL/6小鼠PD模型,采用均匀设计"5因素8水平"分组设计,以小鼠纹状体多巴胺(DA)含量为指标,经回归分析获得最佳配比即优选处方。再应用上述小鼠模型验证优选处方的抗PD药效,检测指标包括:小鼠行为学变化、纹状体DA含量、黑质苏木精-伊红(HE)病理染色和酪氨酸羟化酶(TH)表达情况。结果:经筛选实验得最佳配比处方:多巴丝肼片10 mg/kg,天麻2 g/kg,龟甲2. 4 g/kg,川芎0. 25 g/kg,白芍0. 45 g/kg。与正常对照组比较,模型对照组小鼠爬杆时间显著延长、悬挂时间显著缩短及自主活动计数显著减少,纹状体DA含量明显降低,中脑黑质TH阳性细胞数显著减少(P <0. 05或P <0. 01);与模型对照组比较,龟芍平颤方5. 1 g/kg+多巴丝肼片10 mg/kg组(优选处方)在检测第7 d及之后小鼠爬杆时间显著缩短、悬挂时间显著延长及自主活动计数显著增加,DA含量显著升高,TH表达情况有明显改善(P <0. 05或P <0. 01)。结论:运用均匀设计筛选获得的优选处方对MPTP诱导的小鼠帕金森病具有显著的防治作用。Objective: To screen the dose and proportion of Guishaopingchan compound with Levodopa and Benserazide Hydrochloride to prevent and treat Parkinson’s disease( PD) based on uniform design method,and verified by the animal model. Methods: Guishaopingchan compound( Baishao,Guijia,Tianma,Chuanxiong) and Levodopa and Benserazide Hydrochloride were screened and selected,’5 factors and 8levels’ group design was adopted,C57 BL/6 mice PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine( MPTP) was established. Dopamine( DA) content in mouse striatum was used as the screening index,then regression analysis was applied to obtain the optimal dose of Guishaopingchan compound with Levodopa and Benserazide Hydrochloride,which would be the optimal prescription. The anti PD effect of the optimal prescription was verified by the above mice model,and the detection indexes included behavioral changes,striatal DA content,hematoxylin-eosin( HE) pathological staining and tyrosine hydroxylase( TH) expression. Results: The optimal prescription was obtained through the screening experiment: 10 mg/kg of Levodopa and Benserazide Hydrochloride,2 g/kg of Tianma,2. 4 g/kg of Guijia,0.25 g/kg of Chuanxiong and 0. 45 g/kg of Baishao. Compared with the control group,the climbing time in the model group was prolonged,the suspension time was shortened and the voluntary activity count was decreased,the content of DA in striatum was significantly decreased,and the number of TH positive cells in substantia nigra was significantly decreased( P < 0. 05 or P < 0. 01). Compared with the model group,the optimal prescription decreased the climbing time,prolonged the hanging time and increased the autonomic activity count from the 7 th day. It also increased DA striatum content and significantly improved the expression of TH in the midbrain( P < 0. 05 or P < 0. 01). Conclusion:The optimal prescription obtained by uniform design has the positive effect on preventing and treating PD induced by MPTP.

关 键 词：龟芍平颤方 多巴丝肼片 帕金森病 均匀设计 多巴胺 酪氨酸羟化酶 

分 类 号：R285.5[医药卫生—中药学]