中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2014年
9期
1622-1632
,共11页
高俊鹏%周子懿%向军%陈依萍%蔡定芳
高俊鵬%週子懿%嚮軍%陳依萍%蔡定芳
고준붕%주자의%향군%진의평%채정방
帕金森病%线粒体复合体I%辅酶Q10%小神经胶质细胞%美满霉素%多巴胺能神经元
帕金森病%線粒體複閤體I%輔酶Q10%小神經膠質細胞%美滿黴素%多巴胺能神經元
파금삼병%선립체복합체I%보매Q10%소신경효질세포%미만매소%다파알능신경원
Parkinson disease%Mitochondrial complex I%Coenzyme Q10%Microglia%Minocycline%Dopami-nergic neuron
目的:探讨辅酶Q10与美满霉素联合干预1-甲基-4-苯基吡啶( MPP+)帕金森病模型大鼠的效果。方法:采用MPP+黑质内注射建立帕金森病大鼠模型。小胶质细胞活化的程度用OX-42(小胶质细胞标志物)的免疫荧光强度测定。多巴胺能神经元由酪氨酸羟化酶( TH)阳性神经元的数目确定。大鼠行为学通过阿朴吗啡诱导的旋转行为、前肢跨步运动实验和触须引发的不对称放置实验进行评价。结果:辅酶Q10造模前给药与美满霉素造模后给药均可部分减轻MPP+诱导的帕金森模型鼠行为学缺陷,两者联合给药的效果优于任何一种单一给药方式(均P<0.01),免疫组化分析表明,TH阳性神经元数量在联合给药组中较美满霉素干预组(P<0.01)及辅酶Q10干预组(P<0.01)均显著增多。结论:美满霉素与辅酶Q10联合给药较任何一种单一给药方式对MPP+帕金森病大鼠模型具有更好的神经保护作用,这种针对帕金森病发病过程中不同的病理环节所采取的联合给药方式可能对该病的治疗提供新的思路。
目的:探討輔酶Q10與美滿黴素聯閤榦預1-甲基-4-苯基吡啶( MPP+)帕金森病模型大鼠的效果。方法:採用MPP+黑質內註射建立帕金森病大鼠模型。小膠質細胞活化的程度用OX-42(小膠質細胞標誌物)的免疫熒光彊度測定。多巴胺能神經元由酪氨痠羥化酶( TH)暘性神經元的數目確定。大鼠行為學通過阿樸嗎啡誘導的鏇轉行為、前肢跨步運動實驗和觸鬚引髮的不對稱放置實驗進行評價。結果:輔酶Q10造模前給藥與美滿黴素造模後給藥均可部分減輕MPP+誘導的帕金森模型鼠行為學缺陷,兩者聯閤給藥的效果優于任何一種單一給藥方式(均P<0.01),免疫組化分析錶明,TH暘性神經元數量在聯閤給藥組中較美滿黴素榦預組(P<0.01)及輔酶Q10榦預組(P<0.01)均顯著增多。結論:美滿黴素與輔酶Q10聯閤給藥較任何一種單一給藥方式對MPP+帕金森病大鼠模型具有更好的神經保護作用,這種針對帕金森病髮病過程中不同的病理環節所採取的聯閤給藥方式可能對該病的治療提供新的思路。
목적:탐토보매Q10여미만매소연합간예1-갑기-4-분기필정( MPP+)파금삼병모형대서적효과。방법:채용MPP+흑질내주사건립파금삼병대서모형。소효질세포활화적정도용OX-42(소효질세포표지물)적면역형광강도측정。다파알능신경원유락안산간화매( TH)양성신경원적수목학정。대서행위학통과아박마배유도적선전행위、전지과보운동실험화촉수인발적불대칭방치실험진행평개。결과:보매Q10조모전급약여미만매소조모후급약균가부분감경MPP+유도적파금삼모형서행위학결함,량자연합급약적효과우우임하일충단일급약방식(균P<0.01),면역조화분석표명,TH양성신경원수량재연합급약조중교미만매소간예조(P<0.01)급보매Q10간예조(P<0.01)균현저증다。결론:미만매소여보매Q10연합급약교임하일충단일급약방식대MPP+파금삼병대서모형구유경호적신경보호작용,저충침대파금삼병발병과정중불동적병리배절소채취적연합급약방식가능대해병적치료제공신적사로。
AIM:To investigate the integrative treatment of both coenzyme Q 10 ( CoQ10 ) and minocycline in the rats intranigrally intoxicated with 1-methyl-4-phenylpyridinium ( MPP+) .METHODS:The rat model of Parkinson disease ( PD) was established by intranigral microinjection of MPP +.The degree of microglial activation was measured by immuno-fluorescent density of OX-42 ( a microglia marker ) in the substantia nigra ( SN) .The number of viable dopaminergic neurons was determined by counting the tyrosine hydroxylase ( TH) positive neurons in the SN .The behavioral performances were re-vealed with the number of apomorphine-induced rotations , score of forelimb akinesia and vibrissae-elicited forelimb placing a-symmetry.RESULTS:Pretreatment with CoQ10 or intracerebroventricular (icv) posttreatment with minocycline alone pro-vided partial attenuation against MPP +-induced locomotor defects .Integrative therapy provided enhanced beneficial effects , and resulted in a significant attenuation of locomotor disability than any single therapy (all P<0.01).The results of immu-nohistological analysis showed that the TH positive neurons were maximally protected by integrative therapy compared with minocycline group and CoQ 10 group (P<0.01) .CONCLUSION:The integrative therapy of CoQ 10 combined with minocy-cline may offer additional therapeutic benefit to MPP +-induced hemiparkinson rat model .Such neuroprotective strategy of tar-geting different aspect of the neurodegenerative phenotypes may highlight a new therapeutic strategy for future management of PD.