α-硫辛酸促进帕金森病大鼠黑质细胞铁转出的机制  

Mechanism of α-lipoic acid promoting iron efflux in substantia nigra cells of Parkinson's disease rats

作　　者：蔡婷 魏操 翟素珍[3] 邰胜燕 张春林[3] 焦玲 CAI Ting1,2, WEI Cao3 , ZHAI Suzhen3 , TAI Shengyan3 , ZHANG Chunlin3. , JIAO Ling1, 2(1.Affdiated Hospital of Neurology, 2Department of Neurology, 3Department of Biology, Guizhou Medical University, Guiyang 550004, Chin)

机构地区：[1]贵州医科大学附属医院神经内科,贵州贵阳550004 [2]贵州医科大学神经病学教研室,贵州贵阳550004 [3]贵州医科大学生物学教研室,贵州贵阳550004

出　　处：《细胞与分子免疫学杂志》2018年第1期35-40,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：贵州省科技合作计划(黔科合LH字{2015}7414号);贵阳市科技计划项目(筑科合同[2017]30-30号)

摘　　要：目的检测α-硫辛酸(α-LA)对帕金森病(PD)模型大鼠中脑黑质的铁调节蛋白2(IRP2)、膜铁转运蛋白1(FP1)表达的影响,探讨α-LA在PD模型大鼠黑质调节铁转出的机制。方法健康雄性SD大鼠60只,随机分为假手术组(n=15)、模型组(n=45)。采用立体定位技术将6-羟基多巴胺(6-OHDA)注入大鼠右侧纹状体建立PD模型,假手术组注入同等量的生理盐水。4周后,取30只模型大鼠随机分为PD模型组(n=15)和PD治疗组(n=15)。PD治疗组腹腔注射α-LA 50 mg/(kg·d),连续2周,PD模型组给予同等量生理盐水。治疗14 d后,用圆筒试验(cylinder test)测试大鼠左前肢的使用率;取各组大鼠右侧中脑黑质,采用免疫组织化学染色法检测酪氨酸羟化酶(TH)的表达和分布,采用普鲁士蓝染色法检测铁阳性细胞的数量变化,采用Western blot法检测IRP2和FP1的水平。结果与假手术组相比,PD模型组左前肢使用率显著降低;TH阳性细胞数明显减少,黑质铁阳性细胞数量明显增加;IRP2水平明显增加,FP1水平降低。与PD模型组相比,PD治疗组左前肢使用率明显增加;TH阳性细胞数明显增加,黑质铁阳性细胞数量明显减少;IRP2水平降低,FP1水平增加。结论α-LA能够下调IRP2水平,通过IRP2/IRE通路,上调FP1水平,促进细胞对铁离子的转出,降低PD模型大鼠黑质的铁沉积,减轻6-OHDA诱导的PD模型大鼠脑损伤。Objective To observe the effect of α-lipoic acid （α-LA） on the expressions of iron regulatory protein 2 （IRP2） and ferroportin1 （FP1） in substantia nigra of rats with Parkinson＇s disease （PD） and explore the mechanism by which α-LA regulates iron efflux in substantia nigra cells of PD rat models. Methods Sixty healthy male SD rats were randomly divided into a sham group （ n = 15） and a model group （ n =45）. To establish the PD model, the rats of the model group were injected with 6-hydroxydopamine （6-OHDA） into their right striatum by the stereotactic technique, and the sham operation group was injected with the same dose of normal saline. Four weeks later, 30 model rats were randomly picked and divided into a PD model group （ n = 15） and a PD treatment group （ n = 15）. The PD treatment group was intraperitoneally injected with α-LA （50 mg/kg） daily for 2 weeks, and the PD model group was given the same dose of saline. After 14 days of treatment, the left forelimb use rate was tested by cylinder test. The right middle cerebral substantia nigra was taken from each group, and the expression and distribution of tyrosine hydroxylase （TH） was detected by immunohistochemical staining; the number of iron positive cells was determined by Prussian blue staining; and the levels of IRP2 and FP1 were examined by Western blotting. Results Compared with the sham operation group, the left forelimb use rate of the PD model group was significantly reduced. The number of TH positive cells significantly decreased, and the number of iron positive cells in the substantia nigra significantly increased. The level of IRP2 significantly increased, and the level of FP1 decreased remarkably. Compared with PD model group, the left forelimb use rate of the PD treatment group was significantly raised.The number of TH positive cells was significantly elevated, and the number of iron positive cells in the substantia nigra was significantly reduced. The IRP2 level decreased and the FP1 level incr

关 键 词：帕金森病 Α-硫辛酸 α-羟基多巴胺 铁调节蛋白2(IRP2) 膜铁转运蛋白1(FP1) 

分 类 号：R392.33[医药卫生—免疫学] R742[医药卫生—基础医学]