年龄对MPTP作用于快速老化小鼠SAMP8环氧化酶2表达的影响  

Impact of Age on Cyclooxygenase-2 Expression in Senescence-accelerated Mouse Prone 8 Treated with MPTP

作　　者：张忠霞[1] 马晓伟[1] 顾平[1] 李晓丽[1] 王彦永[1] 王铭维[1] 

机构地区：[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,石家庄050031

出　　处：《中国医科大学学报》2013年第8期697-701,共5页Journal of China Medical University

基　　金：河北省医学科学研究重点课题计划(20110302)

摘　　要：目的探讨1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)对不同年龄快速老化小鼠(SAMP8)急性损伤后黑质纹状体系统多巴胺(DA)含量及环氧化酶2(COX-2)表达影响。方法选用健康雌性SAMP8小鼠(3、6、10月龄各36只),随机分为对照组和用药组。用药组小鼠背部皮下注射MPTP(14 mg.kg-1),每2 h注射1次,共注射4次,制成急性损伤模型;对照组小鼠给予等量生理盐水。分别于第1次给药后1、3、7 d处死小鼠。采用行为学测试观察其运动功能,高效液相色谱法检测黑质DA含量,逆转录聚合酶链反应(RT-PCR)检测纹状体COX-2的表达,观察各时间点MPTP对不同月龄SAMP8小鼠的影响。结果给予MPTP后1、3、7 d,SAMP8小鼠在滚轴上停留时间缩短,DA水平下降,与对照组比较差异有统计学意义(P<0.05);与3、6月龄小鼠比较,10月龄小鼠下降更明显;各用药组小鼠不同时间点COX-2表达均明显增高(P<0.05);10月龄小鼠比3、6月龄升高更显著(P<0.05)。结论衰老是影响帕金森病的重要因素,与环境毒素起到了协同作用;COX-2参与了MPTP所致帕金森病(PD)模型早期急性损伤后的病理反应过程,其反应程度与年龄有关,并随PD发展呈动态改变。Objective To explore the influence of aging on the nigro-strital dopamine（DA） levels and expression of cyclooxygenase-2（COX-2）in the senescence-accelerated mouse prone 8（SAMP8）after an acute intoxication of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）.Methods Healthy female SAMP8 mice of 3,6 and 10-month old（36 mice at each age）were used for the study,and the mice of each age were randomly divided into control group and MPTP group.Acute injury was made by four subcutaneous injection of MPTP（14 mg/kg for every time）with a 2-h interval,while a corresponding volume of saline was given to the control mice.On days 1,3 and 7 after the first injection,all the animals were tested on the rotarod apparatus.After the scarification,the changes of dopamine（DA）in nigro-striatal system was measured by a high performance liquid chromatography with electochemical detector（HPLC-ECD）,and the mRNA expression of COX-2 was determined by reverse transcription-polymerase chain reaction（RT-PCR）.Results Compared with control group,the DA levels and motor activity decreased after MPTP treatment in all SAMP8 mice of different ages,while the expression of COX-2 in tissue was remarkably increased（P 0.05）.Moreover,the changes in the 10-month group were significantly higher than the other two groups（P 0.05）.In addition,the COX-2 became noticeable by day 1,peaked at day 3,and persisted for at least 7 days.Conclusion The results of present study provide evidence that aging plays an important role in the pathology of Parkinson disease（PD）and affects the process together with toxin.COX-2 is involved in the development of PD with dynamical change of the expression,,and the reaction degree is age-related.

关 键 词：1-甲基-4-苯基-1 2 3 6-四氢吡啶 年龄 快速老化小鼠 环氧化酶2 帕金森病 

分 类 号：R741[医药卫生—神经病学与精神病学]