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雷沙吉兰对MPTP诱发急性帕金森病小鼠模型的神经保护和行为学改善作用

颜瑞佐, 郭宝剑, 于沛, 张在军

颜瑞佐, 郭宝剑, 于沛, 张在军. 雷沙吉兰对MPTP诱发急性帕金森病小鼠模型的神经保护和行为学改善作用[J]. 中国药科大学学报, 2016, 47(5): 603-608. DOI: 10.11665/j.issn.1000-5048.20160517
引用本文: 颜瑞佐, 郭宝剑, 于沛, 张在军. 雷沙吉兰对MPTP诱发急性帕金森病小鼠模型的神经保护和行为学改善作用[J]. 中国药科大学学报, 2016, 47(5): 603-608. DOI: 10.11665/j.issn.1000-5048.20160517
YAN Ruizuo, GUO Baojian, YU Pei, ZHANG Zaijun. Effect of rasagiline on neuroprotection and behavior improvement in MPTP-induced acute mouse model of Parkinson′s disease[J]. Journal of China Pharmaceutical University, 2016, 47(5): 603-608. DOI: 10.11665/j.issn.1000-5048.20160517
Citation: YAN Ruizuo, GUO Baojian, YU Pei, ZHANG Zaijun. Effect of rasagiline on neuroprotection and behavior improvement in MPTP-induced acute mouse model of Parkinson′s disease[J]. Journal of China Pharmaceutical University, 2016, 47(5): 603-608. DOI: 10.11665/j.issn.1000-5048.20160517

雷沙吉兰对MPTP诱发急性帕金森病小鼠模型的神经保护和行为学改善作用

基金项目: 国家“重大新药创制”科技重大专项资助项目(No.2010ZX09103-101-055)

Effect of rasagiline on neuroprotection and behavior improvement in MPTP-induced acute mouse model of Parkinson′s disease

  • 摘要: 通过免疫组化方法检测黑质酪氨酸羟化酶阳性神经元的变化,HPLC-ECD检测纹状体内多巴胺(DA)及其代谢产物含量变化,Western blot检测黑质酪氨酸羟化酶的表达,探讨雷沙吉兰对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发C57BL/6小鼠帕金森病模型的疗效和行为学影响。结果显示,腹腔注射MPTP的小鼠出现一系列的急性行为学改变,雷沙吉兰(20 mg/kg)治疗后黑质致密部酪氨酸羟化酶阳性细胞数目较模型组显著增加,纹状体内DA及DA代谢产物HVA和DOPAC含量也明显升高,雷沙吉兰明显改善MPTP诱导帕金森小鼠的运动行为学障碍,对帕金森小鼠模型的多巴胺系统具有保护作用。
    Abstract: This study aimed at investigating the neuroprotective effect and behavior improvement of rasagiline on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP)model mice of Parkinson′s disease. The tyrosine hydroxylase(TH)-positive dopaminergic neurons in substantia nigra were observed by immunocytochemistry. HPLC-ECD was used to detect the dopamine and its metabolite levels. Western blot was used to examine the protein expression of TH. The results showed that the mice appeared a series of acute behavior change after the injection of MPTP. Rasagiline(20 mg/kg)exerted significant protection against MPTP-induced loss of TH-positive dopaminergic neurons. The TH-positive neurons in rasagiline-treated mice brain increased significantly compared with those of MPTP-treated group. Rasagiline also enhanced dopamine and its metabolite levels in striatum significantly. In conclusion, rasagiline has protective effect on the acute mouse model of MPTP-induced Parkinsonism.
  • [1] Qu D, Rashidian J, Mount MP, et al. Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson′s disease[J].Neuron,2007,55(1):37-52.
    [2] Gu X,Zhang Y,Song M,et al.Food effects on the human pharmacokinetics of rasagiline mesylate[J].J China Pharm Univ(中国药科大学学报),2013,44(1):85-88.
    [3] Lai DX,Guo BJ,Cheng JH,et al.Effect of selegiline on athletic ability in Parkinson′s disease in mice[J].Cent South Pharm(中南药学),2013,11(6):421-424.
    [4] Jackson-Lewis V,Przedborski S.Protocol for the MPTP mouse model of Parkinson′s disease[J].Nat Protoc,2007,2(1):141-151.
    [5] Guo B,Xu D,Duan H,et al.Therapeutic effects of multifunctional tetramethylpyrazine nitrone on models of Parkinson′s disease in vitro and in vivo[J].Biol Pharm Bull,2014,37(2):274-285.
    [6] Richter F,Richter A.Chronic rotenone treatment induces behavioral effects but no pathological signs of parkinsonism in mice[J].J Neurosci Res,2007,85(3):681-691.
    [7] He XJ,Yamauchi H,Uetsuka K,et al.Neurotoxicity of MPTP to migrating neuroblasts:studies in acute and subacute mouse models of Parkinson′s disease[J].Neurotoxicology,2008,29(3):413-420.
    [8] Yokoyama H,Takagi S,Watanabe Y,et al.Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice[J].J Neural Transm,2008,115(6):831-842.
    [9] Ferro MM,Bellissimo MI,Anselmo-Franci JA,et al.Comparison of bilaterally 6-OHDA-and MPTP-lesioned rats as models of the early phase of Parkinson′s disease:histological,neurochemical,motor and memory alterations[J].J Neurosci Methods,2005,148(1):78-87.
    [10] Gal S,Zheng H,Fridkin M,et al.Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases.In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion[J].J Neuro Chem,2005,95(1):79-88.
    [11] Li JW,Hu GX,Wang P,et al.Rapid determination of dopamine and its metabolites by HPLC-ECD in mice[J].Guangdong Trace Element Sci(广东微量元素科学),2012,18(11):32-36.
    [12] Salvatore MF,Waymire JC,Haycock JW. Depolarization-stimulated catecholamine biosynthesis:involvement of protein kinases and tyrosine hydroxylase phosphorylation sites in situ[J].J Neurochem,2001,79(2):349-360.
    [13] Matsuura K,Kabuto H,Makino H,et al.Pole test is a useful method for evaluating the mouse movement disorder caused by striatal dopamine depletion[J].J Neurosci Methods,1997,73(1):45-48.
    [14] Gerlach M,Riederer P.Animal models of Parkinson′s disease:an empirical comparison with the phenomenology of the disease in man[J].J Neural Transm,1996,103(8/9):987-1041.
    [15] Tillerson JL,Caudle WM,Reverón ME,et al.Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson′s disease[J].Neuroscience,2003,119(3):899-911.
    [16] Weissman J,Trevor A,Chiba K,et al.Metabolism of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by liver homogenate fractions[J].J Med Chem,1985,28(8):997-1001.
    [17] Yao QH,Gao GD.Behavioral characteristics in mice models of Parkinson′s disease and its detecting method[J].Chin J Clin Rehabil(中国临床康复),2004,8(28):6177-6179.
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  • 刊出日期:  2016-10-24

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