α-硫辛酸对帕金森病大鼠脑内黑质多巴胺能神经元保护机制研究  

Protecive effects of alpha-lipoic acid on brain substantia nigra dopaminergic neurons in rats with Parkinson's disease and its action mechanism

作　　者：吴艳芬[1] 陈文[1] 王鸣飞[2] 王伟[3] 

机构地区：[1]河北省邯郸市第一医院内分泌科,056001 [2]河北省邯郸市妇幼保健院 [3]河北省邯郸市第一医院神经内科,056001

出　　处：《河北医药》2017年第14期2105-2108,2112,共5页Hebei Medical Journal

基　　金：河北省邯郸市科学技术研究与发展计划项目(编号:1423108128)

摘　　要：目的探讨α-硫辛酸(LA)对帕金森病(PD)大鼠模型脑内黑质多巴胺能神经元的保护机制。方法60只3月龄雄性Wistar大鼠随机分为对照组、实验组和药物干预组,每组20只。对照组大鼠给予背部皮下注射葵花油,实验组和药物干预组背部皮下注射鱼藤酮制备PD模型,药物干预组大鼠同时给予LA腹腔注射;采用Western blot检测大鼠中脑多巴胺能神经元中酪氨酸羟化酶(TH)、转录因子NF-E2相关因子-抗氧化反应元件(Nrf2-ARE)和血红素氧合酶1(HO-1)的表达变化;采用分光光度法检测大鼠脑内纹状体中丙二醛(MDA)和还原型谷胱甘肽(GSH)含量变化。结果实验组大鼠中脑TH蛋白表达比对照组明显降低(P<0.05);药物干预组中脑TH蛋白在黑质比鱼藤酮组明显增高(P<0.05),但是较对照组仍有明显减少(P<0.05)。实验组大鼠Nrf2和HO-1蛋白表达比对照组明显降低(P<0.05);药物干预组Nrf2和HO-1蛋白表达比实验组明显增高(P<0.05),但是较对照组仍有明显降低(P<0.05)。与对照组相比,实验组大鼠纹状体组织中脂质代谢产物MDA含量明显增加(P<0.01),药物干预后纹状体中MDA含量明显减少(P<0.05),但较对照组仍明显增高(P<0.05)。与对照组相比,实验组大鼠GSH的含量明显减少(P<0.01),药物干预后GSH明显增加(P<0.05),但较对照组仍显著降低(P<0.05)。结论 LA能激活Nrf2-ARE信号通路对PD大鼠模型中脑多巴胺能神经元起到有效的神经保护作用,改善PD样症状。Objective To investigate the protecive effects of alpha-lipoic acid（ LA） on brain substantia nigra dopaminergic neurons in rats with Parkinson ＇s disease（ PD） induced by rotenone,and to explore its action mechanism.Methods Sixty healthy male Wistar rats（ 3-month age） were randomly divided into three groups： control group,experimental group and drug intervention group,with 20 rats in each group. The rats in control group were given sunflower oil by subcutaneous injection, however,the rats in experimental group and drug intervention group were given rotenone by subcutaneous injection to establish PD models,moreover,the rats in drug intervention group were given LA simultaneously by peritoneal injection. The expression levels of tyrosine hydroxylase（ TH）, transcription factor NF-E2 related factors,anti-oxidant response elements（ Nrf2-ARE） and heme oxygenase 1（ HO-1） in brain substantia nigra of rats were detected by Western Blot,moreover,the levels of malondialdehyde（ MDA） and reduced glutathione（ GSH） in brain striatum of rats were detected by spectrophotometric method. Results The expression levels of TH protein in mesencephalon of rats in experimental group were significantly lower than those in control group（ P 〈0. 05）,however,the expression levels of TH protein in brain substantia nigra of rats in drug intervention group were significantly higher than those in experimental group（ P〈 0. 05）,but which in drug intervention group were significantly lower than those in control group（ P 〈0. 05）. The expression levels of Nrf2 and HO-1 protein in experimental group were significantly lower than those in control group（ P〈 0. 05）,however,which in drug intervention group were significantly higher than those in experimental group（ P〈 0. 05）,moreover,which in drug intervention group were significantly lower than those in control group（ P〈 0. 05）. As compared with those in control group,the levels of MDA in striatum tissues of rats in experimental group

关 键 词：帕金森病 Α-硫辛酸 氧化应激 转录因子NF-E2相关因子-抗氧化反应元件 血红素氧合酶1 

分 类 号：R742.502[医药卫生—神经病学与精神病学]