重组人促红细胞生成素预处理对黑质多巴胺神经元生存预后的影响及其作用机制的研究  

Experimental study on effect and mechanism of preconditioning with recombinant human erythropoietin on prognosis of dopaminergic neurons in substantia nigra of Parkinson disease model induced by 6-hydroxydopamine in vitro

作　　者：陈宏[1] 李红戈[1] 梅元武[1] 曹非[1] 王芳[2] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430022 [2]华中科技大学同济医学院组胚教研室

出　　处：《卒中与神经疾病》2008年第4期204-208,共5页Stroke and Nervous Diseases

摘　　要：目的研究重组人促红细胞生成素(recombinant humane rythropoietin,rhEPO)预处理对帕金森病模型中黑质多巴胺神经元的影响及其作用的机制。方法6-羟多巴胺浸泡大鼠黑质脑片建立离体帕金森病模型,用不同浓度rhEPO在不同时间点预处理黑质多巴胺神经元,观察黑质中酪氨酸羟化酶及氧化应激指标—丙二醛、谷胱甘肽、超氧化物歧化酶和谷胱甘肽过氧化物酶的变化。结果rhEPO预处理能抑制6-羟多巴胺导致的黑质酪氨酸羟化酶阳性细胞数减少,6μ/ml rhEPO预处理在3h与6h时间点的作用优于1μ/mlrhEPO预处理(P<0.01,P<0.05);与6-羟多巴胺组相比,6μ/ml rhEPO预处理组的丙二醛值降低,谷胱甘肽、超氧化物歧化酶、谷胱甘肽过氧化物酶值增高。结论rhEPO预处理对黑质多巴胺神经元具有保护作用,其机制可能与氧化应激反应有关。Objective To study the effect and the mechanism of preconditioning with recombinant human erythropoietin （rhEPO） on the survival of doparninergic（DA） neurons in substantia nigra（SN） of Parkinson disease （PD） models induced by 6-hydroxydopamine（60HDA） in vitro. Methods PD models in vitro were established by incubating rat midbrain slices containing SN in artificial cerebrospinal fluid Ⅱ （ACSF Ⅱ ） containing 6-OHDA （0. 05 mM）. The midbrain slices were preconditioned with the different concentration of rhEPO for different duration. Then observe the change of the number of tyrosine hydroxylase-immunoreactive （TH-IR） positive neurons, maleic dialdehyde（MDA）, glutathione（GSH）, superoxide dismutase （SOD） and glutathione peroxidase （GSH PX） between the different groups. Results The protection of the preconditioning group with rhEPO at concentration of 6μ/ml, where the midbrain slices were incubated for 3 hours or 6 hours, is superior to the protection of the preconditioning group with rhEPO at concentration of 1 μ/ml where the midbrain slices were incubated for 3 hours or 6 hours （P〈0. 01, P〈0. 05, respectively）. The MDA decreased and GSH, SOD and GSH-PX were increased in the preconditioning group with rhEPO at concentration of 6 μ/ml when compared with those in the 6-OHDA group. Conclusions Preconditioning with rhEPO can in- duce neuropotection of DA neurons in SN of PD models induced by 6-OHDA in vitro, it seemed likely that the protection of rhEPO is due to ameliorating oxidative stress.

关 键 词：重组人促红细胞生成素 预处理 帕金森病 氧化应激 6-羟基多巴胺 酪氨酸羟化酶 神经元保护 

分 类 号：R742.5[医药卫生—神经病学与精神病学]