您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2014, Vol. 52 ›› Issue (9): 26-29.doi: 10.6040/j.issn.1671-7554.0.2014.236

• 基础医学 • 上一篇    下一篇

帕金森病模型小鼠黑质纹状体系统氧化应激的增龄性改变

张忠霞, 马晓伟, 王彦永, 李晓丽, 王铭维   

  1. 河北医科大学第一医院神经内科, 河北省脑老化与认知神经科学实验室, 河北 石家庄 050031
  • 收稿日期:2014-03-21 修回日期:2014-06-23 出版日期:2014-09-10 发布日期:2014-09-10
  • 基金资助:
    河北省医学科学研究重点课题计划(20130272,20110302)

Impact of aging on the nigro-strital oxidative stress in a mice model of Parkinson's disease

ZHANG Zhongxia, MA Xiaowei, WANG Yanyong, LI Xiaoli, WANG Mingwei   

  1. Department of Neurology, the First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang 050031, Hebei, China
  • Received:2014-03-21 Revised:2014-06-23 Online:2014-09-10 Published:2014-09-10
  • Contact: 王铭维。E-mail:wmw@hebmu.edu.cn E-mail:wmw@hebmu.edu.cn

摘要: 目的 观察不同月龄小鼠帕金森病(PD)模型黑质纹状体系统氧化应激损伤的增龄性改变并检测老龄PD小鼠氧化应激相关基因的差异性表达。方法 选用健康雌性3、6、10月龄快速老化小鼠P8系(SAMP8)42只,各月龄小鼠随机平均分为MPTP组与对照组,分别给予背部皮下急性注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)及等量0.9%NaCl处理。给药后72 h,采用开放旷场实验观察其运动功能,高效液相色谱法检测黑质DA含量,分光光度计法检测纹状体超氧化物歧化酶(SOD1)活性和丙二醛(MDA)含量,比较不同月龄小鼠黑质DA系统、纹状体氧化应激相关指标损伤的差异。采用PCR Array检测两组10月龄小鼠纹状体氧化应激相关基因表达的差异。结果 与对照组相比,MPTP组各月龄小鼠水平运动距离与站立次数均减少,DA水平、SOD活性明显下降,MDA含量明显增加(P<0.05);与3、6月龄相比,10月龄小鼠上述指标变化更明显;与对照组相比,10月龄MPTP组小鼠环氧化酶-2表达明显上调,而谷胱甘肽过氧化物酶3、6、8,乳酸过氧化物酶、核氧化还原酶、肌红蛋白、神经珠蛋白酶、过氧化物还原酶1和嗜酸粒细胞过氧化物酶9种基因明显下调(倍数改变>2)。结论 月龄是影响PD模型黑质纹状体系统损伤的重要因素;与氧化应激相关的基因的上调或下调可能参与了PD的早期发病。

关键词: 氧化应激, 帕金森病, 快速老化小鼠P8系, 增龄, 基因差异表达

Abstract: Objective To observe the age-related changes of nigro-strital oxidative stress in a mice model of Parkinson's disease(PD) at different ages and detect the differential expression of oxidative stress related genes in aged PD mice by using PCR Array. Methods Forty-two healthy female senescence-accelerated mouse prone 8 (SAMP8) mice aged 3, 6 and 10-month were averagely and randomly divided into 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) group and control group, which were subcutaneously injected with MPTP or the same volum of 0.9% NaCl, respectively. After the first injection for 72 hours, behavioral changes in mice were examined by the open field test. The levels of dopamine (DA) in nigro-striatal system was measured by a high performance liquid chromatography with electochemical detector (HPLC-ECD). The activities of superoxide dismutase 1(SOD1) and the content of malondialdehyde(MDA) were detected by the spectrophotometer. The injuries of nigraldopamine system and striatal oxidative stress related indexes were compared among mice at different ages. The expression of striatal oxidative stress related gene expression in 10-month mice was detected by PCR Array. Results Compared with control group, the levels of DA andSOD 1, the performance in the open field test all decreased in MPTP group at three ages, while the content of MDA in tissue remarkably increased (P<0.01). Moreover, the above changes in 10-month mice were more obvious than 3- and 6-month mice (P<0.05). Compared with control group, the PCR Array results of MPTP group showed that COX-2 was up-regulated, while glutathione peroxidase 3, 6 and 8, lactoperoxidase, nucleoredoxin, myoglobin, neuroglobin, peroxiredoxin 1, eosinophil peroxidase were all down-regulated (fold change>2). Conclusion Aging plays an important role in nigro-striatal system injury of PD model. Up- or down- regulation of oxidative stress related genes may participate in the early phase of PD.

Key words: Oxidative stress, Gene differential expression, Parkinson’s disease, Aging, Senescence-accelerated mouse prone 8

中图分类号: 

  • R741
[1] Van Den Eeden S K, Tanner C M, Bernstein A L, et al. Incidence of Parkinson's disease:variation by age, gender, and race/ethnicity[J]. Am J Epidemiol, 2003, 157(11):1015-1022.
[2] Sowell R A, Owen J B, Butterfield D A. Proteomics in animal models of Alzheimer's and Parkinson's diseases[J]. Ageing ResRev, 2009, 8(1):1-17.
[3] Zhang L, Li Q, Wolff L T, et al. Changes of brain activity in the aged SAMP mouse[J]. Biogerontology, 2007, 8(2):81-88.
[4] Colas D, Gharib A, Bezin L, et al. Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain[J]. BMC Neurosci, 2006, 7:81.
[5] Luchtman D W, Shao D, Song C. Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson's disease[J]. Physiol Behav, 2009, 98(1-2):130-138.
[6] Yamada M, Chiba T, Sasabe J, et al. Nasal Colivelin treatment ameliorates memoryimpairment related to Alzheimer's disease[J]. Neuropsychopharmacology, 2008, 33(8):2020-2032.
[7] 刘萍,罗本燕. 早期帕金森病进展危险因素研究[J]. 中国实用内科杂志, 2013, 33(7):548-551. LIU Ping, LUO Benyan. Risk factors for the progression of early stage Parkinson's disease[J].Chinese Journal of Practical Internal Medicine, 2013, 33(7):548-551.
[8] Yokoyama H, Kuroiwa H, Yano R, et al. Targeting reactive oxygen species, reactive nitrogen species and inflammation in MPTP neurotoxicity and Parkinson's disease[J]. Neurol Sci, 2008, 29(5):293-301.
[9] Sanders L H, Greenamyre J T. Oxidative damage to macromolecules in human Parkinson disease and the rotenone model[J]. Free Radic Biol Med, 2013, 62:111-120. doi:10.1016/j.freeradbiomed.
[10] Liu J, Wang M W, Gu P, et al. Microglial activation and age-related dopaminergic neurodegeneration in MPTP-treated SAMP8 mice[J]. Brain Res, 2010, 1345:213-220. doi:10.1016/j.brainres.2010.05.043.
[11] Nomura Y, Wang B X, Qi S B, et al. Biochemical changes related to aging in the senescence-accelerated mouse[J]. Exp. Gerontol, 1989, 24(1):49-55.
[12] Farr S A, Poon H F, Dogrukol-Ak D, et al. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice[J]. J Neurochem, 2003, 84(5):1173-1183.
[13] Periquet M, Fulga T, Myllykangas L, et al. Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo[J]. J Neurosci, 2007, 27(12):3338-3346.
[14] Wang T, Pei Z, Zhang W, et al. MPP+-induced COX2 activation and subsequent dopaminer gicneurodegeneration[J]. FASEB J, 2005, 19(9):1134-1136.
[1] 江虹,徐晶晶,王瑞,伊向仁,周雅茹,潘芳. 不同年龄阶段老年人的幸福感、心理压力与心理弹性研究[J]. 山东大学学报(医学版), 2017, 55(9): 11-16.
[2] 勾云, 周波, 魏操,陈运华, 徐利,刘芬, 张春林, 文敏. 硫辛酸对帕金森病大鼠黑质线粒体的保护作用[J]. 山东大学学报(医学版), 2017, 55(8): 18-23.
[3] 崔萌,郑冀鲁,田思男,李连军,张琦,金讯波,王慕文. 前列腺绿激光汽化术治疗良性前列腺梗阻伴帕金森病的疗效[J]. 山东大学学报(医学版), 2017, 55(7): 100-102.
[4] 马翔宇,李卫国,陈思,陈腾,李超,徐硕,徐淑军,李新钢. 山东大学齐鲁医院神经外科脑深部电刺激术手术步骤标准化操作流程(SOP)暨核查表[J]. 山东大学学报(医学版), 2017, 55(5): 117-121.
[5] 张文君,沈遥遥,戴庭敏,柴艺轩,涂江龙. 帕金森病并发喉痉挛1例[J]. 山东大学学报(医学版), 2017, 55(5): 125-126.
[6] 王思,李秀华,杜鹃,岳龙涛,王瑶,刘菲,郭配. 侧脑室注射腺病毒介导的GDNF基因对帕金森病的保护作用[J]. 山东大学学报(医学版), 2016, 54(4): 32-36.
[7] 李少伟, 刘宗正, 刘春霞, 张焱如, 周欢敏. 葡萄籽原花青素对小鼠脂肪肝模型缺血再灌注造成的急性肝损伤的保护作用[J]. 山东大学学报(医学版), 2015, 53(9): 41-46.
[8] 郭长艳, 秦雪娇, 吴晓莉, 高雪, 蔡可丽. 线粒体靶向性肽SS-31对H2O2诱导人晶状体上皮细胞凋亡的保护作用[J]. 山东大学学报(医学版), 2015, 53(8): 23-26.
[9] 杨璐, 周英泽, 倪明, 樊秀双, 满建梅, 郭军堂. β-synuclein对Ⅱ型囊泡单胺转移体表达的促进作用[J]. 山东大学学报(医学版), 2015, 53(4): 61-64.
[10] 陈思, 王牧川, 任楠楠, 许巍, 王玲玲, 栾海辉, 马俊, 刘艺鸣. Parkin基因多态性与山东省汉族帕金森病发病风险的关系[J]. 山东大学学报(医学版), 2015, 53(4): 71-74.
[11] 李少伟, 刘宗正, 刘春霞, 张焱如, 周欢敏. 口服富氢水对小鼠脂肪肝缺血再灌注损伤的保护作用[J]. 山东大学学报(医学版), 2015, 53(1): 10-15.
[12] 张静1,暴丽华1,2,吴金涛1,李贵宝1,刘海莉1,岳庆伟1,朱德晓1,孙东1,宋守阳1,丁兆习1,孙晋浩1. 帕金森病肠功能分析及CXCR4在肠神经系统中的表达[J]. 山东大学学报(医学版), 2014, 52(5): 25-29.
[13] 刘莹1,2,王志蕴1,2,解园星1,2,席振创1,2. 瑞舒伐他汀对ApoE-/-小鼠心肌SIRT1信号通路的影响[J]. 山东大学学报(医学版), 2014, 52(3): 7-10.
[14] 孟祥继,庞琦,丁锋,辛涛,杨洪安. 纹状体立体定向注射Taclo建立帕金森病大鼠模型[J]. 山东大学学报(医学版), 2014, 52(3): 16-18.
[15] 杨志英, 刘向春, 关广聚. 蛋氨酸亚砜还原酶B1在糖尿病小鼠肾脏中的表达变化及其与氧化应激的关系[J]. 山东大学学报(医学版), 2014, 52(10): 29-34.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!