百可利对6-羟多巴胺不同注射位点帕金森病模型大鼠的治疗作用  

Effect of baicalein on brain injury induced by 6-hydroxydopamine at different sites in rats

作　　者：何国荣[1] 穆鑫[1] 李晓秀[1] 王月华[1] 方莲花[1] 孙岚[1] 吕扬[2,3] 杜冠华[1,3] 

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]中国医学科学院北京协和医学院药物研究所"晶型药物研究"北京市重点实验室,北京100050 [3]中国医学科学院北京协和医学院药物研究所"天然药物活性物质与功能"国家重点实验室,北京100050

出　　处：《中国药理学通报》2015年第5期623-630,共8页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"科技重大专项"(No2013ZX09102106;2013ZX09508104;2012ZX09301002001001;2013ZX09103001-008;2012ZX09103101-078);国家自然科学基金资助项目(No 81473383)

摘　　要：目的观察百可利对6-羟多巴胺(6-OHDA)内侧前脑束(MFB)和纹状体尾壳核(CPu)两个不同注射位点帕金森病(PD)模型大鼠的治疗作用,两个注射位点模型分别记为:MFB-M,CPu-M。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,制备PD模型。记录大鼠后肢肌电(EMG)信号频率观察肌肉震颤;测定大鼠自主活动;电化学法检测纹状体内多巴胺(DA)及其代谢产物含量;免疫组化法检测大鼠脑内酪氨酸羟化酶(TH)、OX-42表达;观察神经元超微结构变化。结果给药3周后,两个注射位点的模型组行为改变趋势一致,百可利在两个注射位点的模型动物上药效表现不同,在CPu-M组可明显提高PD大鼠自主活动数(P<0.05)。EMG信号分析显示,在MFB-M组,给予百可利,肌电频率降低55%;在CPu-M组,给予百可利,肌电频率降低60%。EMG时效研究表明,在CPu-M组,百可利药效持续420 min以上。纹状体递质水平显示,两个注射位点的模型组DA递质水平差异很大,在CPu-M组,百可利能够明显升高DA水平(P<0.05)。两个注射位点的模型组免疫组织化学结果趋势一致,在CPu-M组,百可利有更明显神经元保护作用(P<0.05),在MFB-M组,百可利抑制小胶质细胞过度激活作用更强(P<0.01)。结论不同注射位点制备的PD模型能够反映不同时期PD的病理变化,百可利可通过抑制炎性介质生成和释放、保护残存神经元、恢复神经元功能等机制改善PD不同发病时期模型动物的行为学症状。Aim To explore the therapeutical effect and mechanism of baicalein on two 6-hydroxydopamine （6-OHDA ） induced Parkinson′s disease （PD ） rat models,which received unilateral lesions of the left medial forebrain bundle （MFB ） or caudate putamen （CPu ） made by stereotaxic injection of 6-OHDA （MFB-M,CPu-M）.Methods PD rat models were＆nbsp;established by microinjection of 6-OHDA into MFB or CPu.The anti-tremor effect of baicalein on PD rat models was examined.Spontaneous activity was recor-ded. Dopamine （DA ）, dihydroxyphenylacetic acid （DOPAC）and homovanilic acid （HVA）in striatum were quantified by HPLC-ECD.The tyrosine hydroxy-lase （TH）and OX-42 positive cells were detected by＆nbsp;immunohistochemical method.The morphological vari-ation of the neurons was confirmed by analysis at an ul-trastructural level.Results Baicalein significantly in-creased the spontaneous activity in CPu-M.The elec-tromyography （EMG ） recordings revealed that com-pared with 6-OHDA group,the tremor frequency in ba-icalein group was decreased by 55% in MFB-M,and by 60% in CPu-M.6-OHDA treatment decreased DA levels in the striatum,while treatment with baicalein attenuated the DA decreases in CPu-M.Moreover,ba-icalein treatment could increase TH-positive neurons and decrease OX-42-postive microglia compared with 6-OHDA group in both MFB-M and CPu-M.Conclu-sions In the present study,it is illustrated that ①microinjection of 6-OHDA into the MFB and the CPu could cause different pathological changes of PD, which is important for efficacy evaluation;②baicalein showed the ability to alleviate the behavior symptoms in PD-rats at different stages by improving motor function and attenuating muscle tremor;③therapeutic effect of baicalein was produced by inhibiting the inflammatory medium production and release,anti-apoptosis,chan-ging dopamine catabolism, and inhibiting dopamine turnover.

关 键 词：百可利 帕金森病 6-羟多巴胺 黑质纹状体通路 内侧前脑束 纹状体尾壳核 神经保护 

分 类 号：R-332[医药卫生] R322.81