中药提取物APD-Ι防治帕金森病运动障碍基础研究  

Basic studies on the prevention and treatment of Chinese medicine extracts APD-Ιon Parkinson′s disease

作　　者：杜仕静 向菊芳 许婷婷 熊静悦[1] 张莉[1] 张秀 李晓媛 谭正怀[1] DU Shijing;XIANG Jufang;XU Tingting;XIONG Jingyue;ZHANG Li;ZHANG Xiu;LI Xiaoyuan;TAN Zhenghuai(Institute of Pharmacology&Toxicology of Chinese Materia Medica,Sichuan Academy of Chinese Medicine Sciences,Chengdu 610041,China;Department of Pharmacy,the Second People′s Hospital of Yibin,Yibin 644000,China)

机构地区：[1]四川省中医药科学院中药药理毒理研究所,四川成都610041 [2]宜宾市第二人民医院药学部,四川宜宾644000

出　　处：《沈阳药科大学学报》2025年第3期253-261,共9页Journal of Shenyang Pharmaceutical University

基　　金：四川省科技厅基本科研业务专项(2021JDKY0013)。

摘　　要：目的探讨中药提取物APD-Ι对帕金森病(Parkinson′s disease,PD)小鼠运动障碍的改善作用及其可能的作用机理。方法采用1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导雄性C57BL/6J小鼠亚急性PD模型研究APD-Ι的预防作用;采用两因素三水平正交试验方法探索APD-Ι和左旋多巴之间在鱼藤酮致PD模型上的交互作用;采用氟哌啶醇致昆明种小鼠PD模型研究APD-Ι对僵住症的预防作用。同时,检测APD-Ι体外对人单胺氧化酶(human monoamine oxidase,hMAO)活性的影响。结果C57BL/6J小鼠连续腹腔注射MPTP 20.0 mg·kg^(-1)19天后,出现爬杆转头时间、爬杆上半段时间、爬杆总时间延长,悬挂评分降低,纵向站立次数减少,横木行走时间增加,与对照组比较差异具有统计学意义;APD-Ι(50、100、300 mg·kg^(-1))能够改善MPTP诱导的PD小鼠运动障碍,与模型组比较差异具有统计学意义。昆明种小鼠连续腹腔注射鱼藤酮3.5 mg·kg^(-1)75天后,出现爬杆时长延长、爬杆评分降低、站立次数减少,与对照组比较差异具有统计学意义;APD-Ι和左旋多巴联用能改善鱼藤酮诱导的PD小鼠的运动障碍,两者在爬杆评分、自发活动纵向站立次数等指标中表现出显著的协同作用。昆明种小鼠腹腔注射氟哌啶醇2.5 mg·kg^(-1)1 h后小鼠僵立率增加和悬网时间显著延长,脑中还原型谷胱甘肽(reduced glutathione,GSH)含量显著降低,与对照组比较差异有统计学意义。APD-Ι(100、300 mg·kg^(-1))小鼠僵立率减少和悬网时间显著缩短,APD-Ι(50 mg·kg^(-1))脑中还原型GSH含量显著升高,与模型组相比较差异有统计学意义。体外测得APD-Ι对hMAO-A和hMAO-B的半数抑制浓度(inhibitory concentration 50,IC50)分别为37.71、62.79μg·mL-1,均是可逆的、竞争性抑制作用。结论APD-Ι防治PD作用与其能够通过血脑屏障到达病灶作用于MAO-B有关,可能也与其具有抗氧�Objective To investigate the effect of APD-I on motor disorders in mice with Parkinson′s disease(PD)and its possible mechanism.Methods The preventive effects of APD-Ιwere investigated using the MPTP-induced subacute PD model in C57BL/6J mice;and a two-factor,three-level orthogonal test was used to explore the interaction between APD-Ιand levodopa on the PD model induced by rotenone in mice;the preventive effects of APD-Ιwere investigated using the haloperidol-induced PD model in Kunming mice.And the effect of APD-Ιon human monoamine oxidase(hMAO)activity was investigated in vitro.Results Motor dysfunction was observed in C57BL/6J mice after continuous intraperitoneal injection of MPTP 20.0 mg·kg^(-1)for 10 days,MPTP 25.0 mg·kg^(-1)for 7 days and MPTP 30.0 mg·kg^(-1)for 5 days.Continuous intraperitoneal injection MPTP 20.0 mg·kg^(-1)for 19 d could prolong the pole climbing time,reduce suspension score and decrease number of standing in C57BL/6J mice.APD-Ι50,100 and 300 mg·kg^(-1)could alleviate the dyskinesia in MPTP treated mice.Rotenone 3.5 mg·kg^(-1)could prolong the pole climbing time,reduce pole climbing score,hanging score and number of standing in Swiss mice;The combination of APD-Ιand levodopa could improve the dyskinesia,and had synergistic effects on pole climbing score and number of spontaneous standing in rotenone-treated mice.After the intraperitoneal injection of haloperidol 2.5 mg·kg^(-1)for 1 h,the rigidity time and suspension time of Kunming mice were significantly prolonged,and the content of GSH in brain was significantly decreased,which had statistical significance compared with the control group.The half-inhibitory concentration(IC50)of APD-Ιon hMAO-A and hMAO-B measured in vitro were 37.71μg·mL-1 or 62.79μg·mL-1.The inhibitory effects of APD-Ιon hMAO-A and hMAO-B were reversible and competitive.Conclusion The effect of APD-Ιin preventing and controlling PD is related to its ability to act on MAO-B through the blood-brain barrier,as well as its ability to protect neural t

关 键 词：帕金森病 运动障碍 僵住症 APD-Ι 单胺氧化酶 

分 类 号：R96[医药卫生—药理学]