P-gp对百草枯诱导慢性帕金森病大鼠模型血脑屏障和多巴胺能神经元的影响  

Effct of P-gp in blood-brain barrier and dopaminergie neurons of rats with paraquat-induced chronic Parkinson's disease

作　　者：孟珊珊[1] 贾非 刘洪文[1] 赵庆杰[3] 张杰[1] 

机构地区：[1]哈尔滨医科大学附属第一医院大桥分院,150076 [2]武警牡丹江市森林支队 [3]哈尔滨医科大学附属第一医院神经内科

出　　处：《卒中与神经疾病》2013年第6期331-335,共5页Stroke and Nervous Diseases

基　　金：黑龙江省教育厅科学技术研究项目(编号12511263)

摘　　要：目的通过观察百草枯诱导的慢性帕金森病大鼠模型中血脑屏障功能和P-糖蛋白表达的变化,探讨百草枯诱导帕金森病的机制;观察P-糖蛋白功能对多巴胺能神经元的影响,进一步探讨P-糖蛋白在百草枯诱导的慢性帕金森病过程中的保护作用。方法将大鼠随机分成5组:对照组、PQ4周组、PQ4周+诱导剂组、PQ4周+抑制剂组和PQ8周组。用免疫组织化学染色方法显示大鼠中脑TH阳性细胞;western blotting检测TH蛋白和P-糖蛋白表达;Belyaevs'法使用EB测定BBB通透性;HPLC-EC法测定纹状体中5-HT、DA、DOPAC和HVA含量。结果百草枯所致的慢性帕金森病大鼠模型(1)TH阳性神经元较对照组明显减少(P<0.05)、TH蛋白和P-gp表达显著降低(P<0.05)、大鼠BBB的通透性显著增加(P<0.05);(2)纹状体内5-HT、DA、DOPAC和HVA含量降低,诱导P-糖蛋白表达能使上述物质含量增加,抑制P-糖蛋白表达能使上述物质含量显著降低(P<0.05)。结论百草枯可能通过增加BBB通透性和降低P-糖蛋白的表达来诱导帕金森病;P-糖蛋白对多巴胺能神经元有保护作用。Objective To explore the pathogenesis of paraquat-induced chronic Parkinson＇s disease by investigating the alteration of blood-brain barrier （BBB） measured by EB and expression of P-gp in a rat model of paraquat-induced chronic Parkinson＇s disease. To observe the relationship among the dopaminergie neurons and P-gp in a rat model of paraquat-induced chronic Parkinson＇s disease, so as to study the protection of P-gp in paraquat-induced chronic Parkinson＇s disease. Methods Fifty male Wistar rats were randomly divided into five groups： physiologic saline group, paraquat 4w group, paraquat 4w ＋ activator group, paraquat 4w ＋ in- hibitor group and paraquat 8w group. The number of tyrosine hydroxylase （TH）-positive neurons were ob- served by immunohistochemistry; TH protein and the P-gp expressions were examined by western blotting; the B1313 permeability was assessed by P, elyaevs＂ method; the content of 5-HT, dopamine and its metabolites （DOPAC and HVA ） were determined by HPLC-EC. Results In the rat model of paraquat-induced chronic Parkinson＇s disease： （1） TH-positive neurons were obviously reduced （P〈0. 05）, TH and P-gp protein ex- pressions were downregulated obviously （P〈0. 05）, the BBB permeability of the model groups was obviously deduced （P〈0. 05） ; （2） the levels of 5-HT, DA, DOPAC and HVA were reduced in the striatum, and could be increased by P-gp activator and be decreased by P-gp inhibitor （P〈0. 05）. Conclusions Paraquat might have certain effect on chronic PD by up-regulating BBB permeability and reducing P-gp protein expression, and P-gp may have neuroprotective effect in the rat model of paraquat-induced chronic Parkinson＇s disease.

关 键 词：帕金森病 百草枯 血脑屏障 P-糖蛋白 多巴胺能神经元 

分 类 号：R742[医药卫生—神经病学与精神病学]