木犀草素联合芦丁抗6-羟多巴胺诱导的帕金森病大鼠震颤及神经保护作用  

Neuroprotective and antitremor effect of the mixture of luteolin and rutin on 6-hydroxydopamine induced Parkinson's disease in rat models

作　　者：何国荣[1] 成银霞[1] 穆鑫[1] 李晓秀[1] 于昕[2] 王月华[1] 方莲花[1] 杜冠华[1] 

机构地区：[1]中国医学科学院,北京协和医学院药物研究所,"药物靶点研究与新药筛选"北京市重点实验室,北京100050 [2]烟台大学药学院药理学教研室,山东烟台264005

出　　处：《中国药理学通报》2012年第5期626-632,共7页Chinese Pharmacological Bulletin

基　　金：国家"重大新药创制"科技重大专项资助项目(No 2009ZX09302-003;2009YZH-LCH07);卫生部公益性行业科研专项资助项目(No 200802041;200902008);科技部基础性工作专项重点项目(No 2007FY130100)

摘　　要：目的探讨木犀草素和芦丁组合物(mixture of luteolinand rutin,MLR)对6-羟多巴胺(6-OHDA)诱导的帕金森病(parkinson's disease,PD)模型大鼠减轻震颤和保护神经元的作用及机制。方法运用6-OHDA两点注射法,损毁大鼠左侧中脑多巴胺能神经元,复制PD模型。2周后,将造模成功大鼠随机分为模型组、美多芭给药组(50 mg·kg-1)、MLR给药组(125、250、375 mg·kg-1),另取手术并注射生理盐水、经检测无旋转运动的大鼠为假手术组。在给药后第3周记录大鼠后肢肌电(EMG),观察肌肉震颤。行为学检查完毕后采用免疫组化法检测大鼠黑质酪氨酸羟化酶(TH)、多巴胺转运体(DAT)、胶质原纤维酸性蛋白(GFAP)阳性细胞数。结果 EMG检测结果显示,MLR各给药组可明显降低大鼠的震颤频率和幅度,中、高剂量组的作用优于美多芭组。免疫组化结果显示,MLR高剂量组TH免疫阳性神经元的数目约为模型组的499.14%,MLR高剂量组GFAP免疫阳性星形胶质细胞的数目比模型组降低了43.68%。结论MLR可剂量依赖性抑制PD模型大鼠震颤,减轻神经元受损程度,抑制星形胶质细胞激活和促炎因子释放,从而延缓DA能神经元进行性退变。Aim To explore the neuroprotective and antitremor effect of the complex mixture of luteolin and rutin（MLR） on 6-hydroxydopamine（6-OHDA）-induced Parkinson＇s disease（PD） in rat models.Methods PD rat models were established by microinjection of 6-OHDA into the left medial forebrain bundle（MFB）.After 2 weeks,the rats were divided into six groups randomly： sham-lesioned rats（control,saline ig）,6-OHDA（saline ig）,madopar（50mg·kg-1 ig）,MLR（125,250,375mg·kg-1 ig）.3 weeks after MLR treatment,the presence of tremors were assessed.The number of tyrosine hydroxylase（TH）,dopamine transport protein（DAT）,and glial fibrillary acidic protein（GFAP） positive cells were detected by immunohistochemical method.Results The Electromyography（EMG） recordings revealed the characteristic of muscle activity,MLR could decrease the burst amplitude and burst frequency.The number of TH-positive neurons in MLR high-dose group was approximately 5 times more than 6-OHDA group and GFAP-postive astrocyte decreased by 43.68% compared with 6-OHDA group.Conclusions MLR can significantly suppress muscle tremor in a dose-dependent manner,and avert neurodegenerative processes.The mechanism of MLR in PD may be related the fact with that it can provide a protective effect against 6-OHDA-induced loss of dopaminergic（DA） neuron,attenuate astrocyte activation and the release of pro-inflammatory factor.

关 键 词：木犀草素 芦丁 帕金森病 6-羟多巴胺 大鼠 震颤 神经保护 

分 类 号：R-332[医药卫生] R284.1