类叶升麻苷对MPTP诱导帕金森病模型小鼠的神经保护作用及其机制  

Neuroprotective effect and mechanism of acteoside on mouse model of MPTP-induced Parkinson's disease

作　　者：田芳 董欣宜 杜冲[3] 高亚娟[4,5] 蒲小平 TIAN Fang;DONG Xin-yi;DU Chong;GAO Ya-juan;PU Xiao-ping(Department of Pharmacy,Tianjin First Central Hospital,Tianjin 300192,China;Department of Pharmacy,Tianjin Medical University Eye Hospital,Tianjin 300384,China;Department of Oncology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China;Department of Radiology,Peking University Third Hospital,Beijing 100191,China;NMPA Key Laboratory for Evaluation of Medical Imaging Equipment and Technique,Beijing 100191,China;Department of Molecular and Cellular Pharmacology,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]天津市第一中心医院药学部,天津300192 [2]天津医科大学眼科医院药剂科,天津300384 [3]西安交通大学第二附属医院肿瘤科,西安710004 [4]北京大学第三医院放射科,北京100191 [5]北京市国家药品监督管理局成像设备质量评价重点实验室,北京100191 [6]北京大学药学院分子与细胞药理学系,北京100191

出　　处：《中国新药杂志》2023年第6期618-624,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(U1603128)。

摘　　要：目的:探究类叶升麻苷(ACT)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠的神经保护作用及其机制。方法:采用腹腔注射MPTP构建PD模型小鼠,实验动物随机分为对照组、模型组和100 mg·kg^(-1)ACT给药组,通过灌胃(ig)的方式连续给药14 d,给药完成后,行为学评价和生化学检测评价ACT对PD小鼠的神经保护作用。采用双向电泳技术、质谱分析技术和Western blot检测进一步对ACT抗PD机制进行探究。结果:ACT预防性给药后明显缩短MPTP诱导PD小鼠的爬杆时间,提高游泳测试评分,延长悬挂持续时间,并降低后肢张力测试评分和圆柱体实验评分。ACT可以有效改善MPTP诱导PD小鼠黑质纹状体组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活性,并降低丙二醛(MDA)的含量。双向电泳和Western blot检测发现胆绿素还原酶B(biliverdin reductase B,BLVRB)在MPTP诱导PD小鼠的黑质纹状体中的表达升高,而ACT给药后显著降低此蛋白的表达。结论:ACT对MPTP诱导的PD小鼠具有神经保护作用,其潜在机制可能与ACT降低BLVRB的表达及抗氧化应激相关。Objective:To explore the neuroprotective effect of acteoside(ACT)on mouse model of MPTPinduced Parkinson's disease(PD)and its mechanism.Methods:The PD mouse model was established by intraperitoneal injection of MPTP.The experimental mice were randomly divided into control group,model group and ACT group(100 mg·kg^(-1)),which were administrated by gavage for 14 d.After administration,behavioral evaluation and biochemical detection were performed to evaluate the neuroprotective effect of ACT on PD mice.Two-dimensional electrophoresis,mass spectrometry and Western blot were used to further explore the anti-PD mechanism of ACT.Results:After prophylactic administration of ACT,the pole climbing time of MPTP-induced PD mice was significantly shortened,swimming test score was improved,suspension duration was prolonged,and hind limb tension test score and cylinder test score were decreased.ACT could effectively improve the activities of SOD,CAT,and GSH-Px in the substantia nigra and striatum of MPTP-induced PD mice and reduce the content of MDA.The results of two-dimensional electrophoresis and Western blot showed that the expression of biliverdin reductase B(BLVRB)increased in the substantia nigra and striatum of PD mice induced by MPTP,while the expression of BLVRB decreased significantly after the administration of ACT.Conclusion:ACT has neuroprotective effect on MPTP-induced PD mice,and its underlying mechanism may be related to the decrease of BLVRB expression and anti-oxidative stress of ACT.

关 键 词：类叶升麻苷 帕金森病 神经保护作用 氧化应激 胆绿素还原酶B 

分 类 号：R965[医药卫生—药理学]