辅酶Q_(10)与美满霉素联合干预1-甲基-4-苯基吡啶诱导的偏侧帕金森病大鼠模型研究(英文)  

Integrative therapy using coenzyme Q_(10) and minocycline in 1- methyl-4-phenylpyridinium- induced hemiparkinson rats

作　　者：高俊鹏[1] 周子懿[2] 向军[3] 陈依萍[3] 蔡定芳[3] 

机构地区：[1]广州医科大学附属广州市第一人民医院中西医结合科,广东广州510160 [2]广州中医药大学附属第二临床医学院脑病一科,广东广州510120 [3]复旦大学附属中山医院中西医结合科,上海200032

出　　处：《中国病理生理杂志》2014年第9期1622-1632,共11页Chinese Journal of Pathophysiology

摘　　要：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。AIM： To investigate the integrative treatment of both coenzyme Q10（ 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 immunofluorescent 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 revealed with the number of apomorphine-induced rotations,score of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry. RESULTS： Pretreatment with CoQ10 or intracerebroventricular（ icv） posttreatment with minocycline alone provided 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 immunohistological analysis showed that the TH positive neurons were maximally protected by integrative therapy compared with minocycline group and CoQ10group（ P〈 0. 01）. CONCLUSION： The integrative therapy of CoQ10 combined with minocycline may offer additional therapeutic benefit to MPP^＋-induced hemiparkinson rat model. Such neuroprotective strategy of targeting different aspect of the neurodegenerative phenotypes may highlight a new therapeutic strategy for future management of PD.

关 键 词：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 

分 类 号：R741[医药卫生—神经病学与精神病学]