6-羟基多巴胺诱导的帕金森病大鼠中脑黑质褪黑素及褪黑素受体的变化  

Changes of melatonin and melatonin receptors on 6-OHDA induced Parkinson＇s disease in rat

作　　者：袁苏涛[1] 杜越群[3] 孟涛[3] 林玲[2,3] 

机构地区：[1]福建医科大学省立临床学院,福州350001 [2]福建医科大学基础医学院神经生物学中心,福州350001 [3]福建医科大学生物化学与分子生物学系,福州350001

出　　处：《中华行为医学与脑科学杂志》2014年第7期580-583,共4页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金资助项目（81241047）;福建省科技计划重点项目（2012Y0031）

摘　　要：目的 观察偏侧帕金森病（PD）大鼠中脑黑质毁损侧（右侧）及健侧（左侧）多巴胺及其代谢产物、以及褪黑素和褪黑素受体的变化.方法 6-羟基多巴胺（6-OHDA）损毁大鼠右侧黑质-纹状体通路制备偏侧PD模型,大鼠分为溶剂对照组和PD组.分别于建模后3周,6周10：00和22：00分离黑质组织,用高效液相色谱检测多巴胺及其代谢产物、以及褪黑素水平的变化,采用RT-PCR,Western-Blot检测PD大鼠毁损侧及健侧黑质褪黑素受体MT1和MT2的表达水平.结果 PD大鼠毁损侧黑质与其健侧相比,建模后3周和6周多巴胺水平分别降低了83％和88％;建模后6周10：00和22：00,PD大鼠毁损侧黑质与其健侧相比,褪黑素水平分别增加了22％和29％.与溶剂对照组双侧黑质相比,PD大鼠健侧黑质褪黑素水平分别增加了46％和31％,毁损侧MT1和MT2的mRNA水平分别降低了91.04％和90.24％ （P＜0.01）,蛋白水平分别降低了58％和70％ （P＜0.01）.结论 6-OHDA诱导的晚期PD大鼠双侧黑质组织褪黑素水平增加,以及毁损侧黑质褪黑素受体表达下调可能与PD的进展有关.Objective To observe the changes of dopamine and its metabolites,melatonin,as well as melatonin receptors in the substantia nigras （SN） in 6-OHDA induced hemiparkinsonian rats.Methods PD rat was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta and medial forebrain bundle.Rats were divided into PD groups and vehicle groups,and sacrificed at 10：00 and 22：00 respectively,at 3 and 6 weeks post-lesion.The contents of dopamine and its metabolites as well as melatonin were measured by HPLC.The expressions of MT1 and MT2 mRNA and protein were detected by RT-PCR and Western-Blot respectively.Results Dopamine levels declined by 83% and 88% respectively at 3 and 6 weeks post-lesion in the injected side of PD rats,compared with the contralateral side.Melatonin levels in the injected side increased by 22% and 29% respectively.However,melatonin increased by 46% and 31% respectively at 10：00 and 22：00,at 6 weeks post-lesion in the contralateral side,compared with the same side of the vehicle.The expressions of MT1 and MT2 receptors mRNA were significantly decreased by 91.04% and 90.24% respectively in comparison with the vehicle,while the protein expression of MT1 and MT2 receptors significantly declined by 58% and 70% respectively.Conclusion Increased melatonin and down-regulated MT1 and MT2 receptors in the lesioned SN in 6-OHDA-induced rats may be associated with the progression of PD.

关 键 词：帕金森病 褪黑素 褪黑素受体 

分 类 号：R742.5[医药卫生—神经病学与精神病学]