异钩藤碱对MPTP所致帕金森病小鼠的疗效研究
Effects of isorhynchophylline on MPTP-induced Parkinson’s disease in mice
- 上海中医药大学学报 2021年35卷第4期 页码：61-66
- 作者机构：
1.广东药科大学药理系（广东 广州 510006）
2.暨南大学药学院（广东 广州 510632）
3.佛山科学技术学院医学院（广东 佛山 528225）
- 作者简介：
陈海云，女，博士，讲师，主要从事神经药理学研究
- 基金信息：国家自然科学基金青年基金资助项目(81803512);广东省自然科学基金博士科研启动项目(2018A030310562);广东省教育厅普通高校科研特色创新类项目(2019ktscx195)
DOI：10.16306/j.1008-861x.2021.04.009
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陈海云, 魏来娇, 曹杰, 等. 异钩藤碱对MPTP所致帕金森病小鼠的疗效研究[J]. 上海中医药大学学报, 2021,35(4):61-66.
CHEN Haiyun, WEI Laijiao, CAO Jie, et al. Effects of isorhynchophylline on MPTP-induced Parkinson’s disease in mice[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(4):61-66.
陈海云, 魏来娇, 曹杰, 等. 异钩藤碱对MPTP所致帕金森病小鼠的疗效研究[J]. 上海中医药大学学报, 2021,35(4):61-66. DOI： 10.16306/j.1008-861x.2021.04.009.
CHEN Haiyun, WEI Laijiao, CAO Jie, et al. Effects of isorhynchophylline on MPTP-induced Parkinson’s disease in mice[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(4):61-66. DOI： 10.16306/j.1008-861x.2021.04.009.
摘要
目的：,2,研究钩藤提取物异钩藤碱（IsoRhy）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。,方法：,2,将C57BL/6小鼠随机分为对照组、MPTP组、雷沙吉兰（Rasagiline，0.1 mg/kg）组和IsoRhy（40 mg/kg）组，每组8只。除对照组外，其他各组小鼠腹腔注射30 mg/kg MPTP，连续5 d，诱导PD模型。实验第8天起，各药物组灌胃给予相应药物，连续2周。末次给药后，小鼠进行行为学测试，再分离脑组织。高效液相色谱－电化学检测法（HPLC-ECD）检测纹状体内多巴胺（DA）及其代谢产物含量；免疫组化检测脑黑质区酪氨酸羟化酶（TH）阳性表达神经元数量，Western blot检测脑黑质区TH蛋白表达。,结果：,2,①爬杆测试：IsoRhy组小鼠的爬杆时间较MPTP组明显减少（,P,<,0.01）。脚印实验：IsoRhy可有效增加模型小鼠的步幅长度（,P,<,0.01），但对走槽时间无明显影响。旷场实验：IsoRhy组小鼠的运动距离较MPTP组显著增加（,P,<,0.01）。转棒实验：IsoRhy组小鼠在棒时间多于MPTP组，但差异无统计学意义（,P,>,0.05）。②IsoRhy组小鼠纹状体内DA及其代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）含量较MPTP组升高，但差异无统计学意义（,P,>,0.05）。③IsoRhy干预2周后，模型小鼠脑黑质区TH阳性表达神经元较MPTP组明显增加（,P,<,0.05），黑质区TH蛋白表达较MPTP组明显升高（,P,<,0.05）。,结论：,2,IsoRhy能够在一定程度上改善MPTP诱导的PD模型小鼠的运动行为学，通过上调脑黑质区TH蛋白表达，减轻多巴胺能神经元损伤。
Abstract
Objective:,2,To investigate the neuroprotective effects of isorhynchophylline(IsoRhy), extract of Uncariae Ramulus Cum Uncis, on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) -induced Parkinson’s disease(PD) model mice.,Methods:,2,C57BL/6 mice were randomly divided into the control group, MPTP group, Rasagiline(0.1 mg/kg) group and IsoRhy(40 mg/kg) group, 8 mice in each group.Except the control group, the other groups were intraperitoneally injected with 30 mg/kg MPTP for 5 days, so as to induce PD model.From the 8th day of the experiment, the drug treatment groups were treated with the corresponding drugs by intragastric administration for two weeks.After the last administration, behavioral tests were performed and brain tissue was separated.The contents of dopamine(DA) and its metabolites in striatum were determined by high performance liquid chromatography with electrochemical detection(HPLC-ECD) .The number of tyrosine hydroxylase(TH) positive neurons in substantia nigra was detected by immunohistochemistry, and the TH protein expression in substantia nigra was detected by Western blot.,Results:,2,①Pole test: The climbing time of mice in the IsoRhy group was significantly shorter than that in the MPTP group(,P,<,0.01) .Footprint test: IsoRhy could effectively increase the stride length of the model mice(,P,<,0.01), but showed no significant effect on the passing time.Open field test: The movement distance of mice in the IsoRhy group was significantly longer than that in the MPTP group(,P,<,0.01) .Rotarod test: The stay time of mice in the IsoRhy group was longer than that in the MPTP group, but with no statistically significant difference(,P,>,0.05) .②The contents of DA and its metabolites 3, 4-dihydroxyphenylacetic acid(DOPAC) and homovanillic acid(HVA) in striatum of the IsoRhy group were higher than those of the MPTP group, but with no statistically significant differences(,P,>,0.05) .③After treatment with IsoRhy for two weeks, the TH positive neurons in substantia nigra of the model mice were significantly increased compared with those in the MPTP group(,P,<,0.05), and the TH protein expression in substantia nigra was significantly higher than that in the MPTP group(,P,<,0.05) .,Conclusion:,2,IsoRhy can improve the motor behavior of MPTP-induced PD model mice to a certain extent, and alleviate the damage of dopaminergic neurons by up-regulating the TH protein expression in substantia nigra.
关键词
异钩藤碱帕金森病MPTP神经保护小鼠
Keywords
isorhynchophyllineParkinson’s diseaseMPTPneuroprotectionmouse
references
KUMAR B，PANDEY M，FAYAZ F，et al. Applications of Exosomes in Targeted Drug Delivery for the Treatment of Parkinson’s Disease：A Review of Recent Advances and Clinical Challenges[J]. Curr Top Med Chem，2020，20(30)：2777-2788.
DORSEY E R，SHERER T，OKUN M S，et al. The Emerging Evidence of the Parkinson Pandemic[J]. J Parkinson Dis，2018，8(S1)：S3-S8.
SCHAPIRA A H，OLANOW C W，GREENAMYRE J T，et al. Slowing of neurodegeneration in Parkinson’s disease and Huntington’s disease：future therapeutic perspectives[J]. Lancet，2014，384(9942)：545-555.
MEISSNER W G，FRASIER M，GASSER T，et al. Priorities in Parkinson’s disease research[J]. Nat Rev Drug Discov，2011，10(5)：377-393.
张雪，张雯，杜立达，等.抗帕金森病药物及其作用靶点研究进展[J].国际药学研究杂志，2016，43(1)：87-96.
张立娟，张倩，王康锋，等.天麻钩藤饮对帕金森病模型大鼠行为学及纹状体内多巴胺含量的影响[J].江苏中医药，2018，50(2)：79-82.
卢芳，井月娥，任燕冬，等.钩藤提取物对MPTP诱导帕金森病模型小鼠神经元的影响[J].中国中医药信息杂志，2016，23(4)：57-60.
YANG W，IP S P，LIU L，et al. Uncaria rhynchophylla and its Major Constituents on Central Nervous System：A Review on Their Pharmacological Actions[J]. Curr Vasc Pharmacol，2020，18(4)：346-357.
JACKSON-LEWIS V，PRZEDBORSKI S. Protocol for the MPTP mouse model of Parkinson’s disease[J]. Nat Protoc，2007，2(1)：141-151.
延沁儒，王春梅.异钩藤碱保护神经系统的药理研究进展[J].遵义医学院学报，2018，41(3)：371-375.
CHEN H，CAO J，ZHA L，et al. Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways[J]. Aging（Albany NY），2020，12(14)：14897-14917.
李军伟，胡国新，王萍.HPLC-ECD法检测小鼠体内多巴胺及其代谢产物[J].广东微量元素科学，2012，18(11)：32-36.
REICH S G，SAVITT J M. Parkinson’s Disease[J]. Med Clin North Am，2019，103(2)：337-350.
ALEXOUDI A，ALEXOUDI I，GATZONIS S. Parkinson’s disease pathogenesis，evolution and alternative pathways：A review[J]. Rev Neurol（Paris），2018，174(10)：699-704.
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