吉林大学学报(医学版)

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丹参酮ⅡA对帕金森病模型小鼠多巴胺能神经元的保护作用及其机制

任博,孙法威,张作凤,张宇新   

  1. (河北联合大学基础医学院人体解剖学教研室,河北 唐山 063000)
  • 收稿日期:2013-12-02 出版日期:2014-09-28 发布日期:2014-09-28
  • 通讯作者: 张宇新 E-mail:(Tel:0315-3726421,E-mail:jpzyx@163.com)
  • 作者简介:任博(1987-),男,山东省济南市人,医学硕士,主要从事帕金森病病因与发病机制的研究。
  • 基金资助:

    河北省科技厅自然科学基金资助课题(C2004000689);河北省科技厅博士基金资助课题 (05547008D-4);河北省 科技厅科学技术与社会发展计划项目资助课题(04276135)

Protective effect of tanshinoneⅡA on dopaminergic neurons in mouse model of Parkinson’s disease and its mechanism

REN Bo,SUN Fa-wei,ZHANG Zuo-feng,ZHANG Yu-xin   

  1. (Department of Anatomy,School of Basic Medical Sciences,Hebei United University,Tangshan 063000,China)
  • Received:2013-12-02 Online:2014-09-28 Published:2014-09-28

摘要:

目的:探讨丹参酮ⅡA对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱发的帕金森病(PD)模型小鼠中脑黑质区多巴胺能神经元损伤的影响,阐明其对多巴胺能神经元的保护作用及其可能机制。 方法:将60只C57BL/6N小鼠随机分为对照组、PD模型组和丹参酮ⅡA组,每组20只。PD模型组和丹参酮ⅡA小鼠采用MPTP制备PD小鼠模型,丹参酮ⅡA组制备PD模型后腹腔注射丹参酮ⅡA,观察各组小鼠行为学表现,采用免疫组织化学、免疫蛋白印迹和免疫荧光双标法检测各组小鼠中脑黑质区酪氨酸羟化酶(TH)、整合素超家族成员Ⅰ型跨膜蛋白(cd11b)、烟酰胺腺嘌呤二核苷酸(NADPH)氧化酶、诱导型一氧化氮合酶(iNOS)阳性细胞数和蛋白表达水平。 结果:与对照组比较,PD模型组小鼠出现典型的PD样症状;PD模型组小鼠中脑黑质区TH阳性神经元数和蛋白表达水平较对照组减少约45%和50%,cd11b、p47-phox和iNOS阳性细胞数和蛋白表达水平增加(P<0.01)。与PD模型组比较,丹参酮ⅡA组小鼠PD样症状减轻,黑质区TH阳性神经元数量和蛋白表达水平明显升高(P<0.01),cd11b、p47-phox和iNOS阳性细胞数明显减少(P<0.01),蛋白表达水平明显降低(P<0.01)。 结论:丹参酮ⅡA可在一定程度上阻抑MPTP诱导的PD模型小鼠中脑黑质区多巴胺能神经元的丢失,其神经保护作用机制可能与抑制小胶质细胞激活、NADPH氧化酶和iNOS表达有关。

关键词: 帕金森病, 小胶质细胞, 烟酰胺腺嘌呤二核苷酸氧化酶, 诱导型一氧化氮合酶, 酪氨酸羟化酶, 丹参酮ⅡA, 小鼠

Abstract:

Abstract:Objective
To explore the effects of tanshinone ⅡA on the injury of dopaminergic neurons of Parkinson’s disease (PD) mouse model induced by 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),and to clarify the possible mechanism of its protective effects on dopaminergic neurons.Methods 60 C57BL/6N mice were randomly divided into control group,PD  model group and tanshinone ⅡA group(n=20).The mice in PD model group and tanshinone ⅡA group were treated with MPTP to establish PD models.The bebavior of the mice  in various groups was observed.The number of tyrosine hydroxylase (TH),cd11b,p47-phox,and inducibleni tricoxidesynthase (iNOS)-positive cells,and the protein expression levels of TH,cd11b,p47-phox and iNOS in the substantia nigra (SN) of the midbrain of the mice in various groups  were detected with immunohistochemistry,Western blotting and double-labeling immunofluorescence assay. Results Compared with control group,the mice  in PD model group exhibited typical symptoms of PD,and the number of TH-positive cells and the protein expression level of TH in the substantia nigra of the mice in PD model group were reduced by about 45% and 50%;the number of cd11b,p47-phox,iNOS-positive cells and the protein expression levels of cd11b,p47-phox,iNOS were markedly increased (P<0.01).Compared with PD model group,the symptoms of PD of the mice in tanshinone ⅡA group were alleviated, the number of TH-positive cells and the expression level of TH protein in the SN were increased(P<0.01),and the number of cd11b,p47-phox and iNOS-positive cells and the TH protein expression levels were obviously decreased(P<0.01).Conclusion Tanshinone ⅡA could mitigate the loss of dopaminergic neurons in the PD mouse model induced by MPTP.The mechanism of neuprotective effect may be related to the inhibition of microglial activation,NADPH oxidase and iNOS expressions.

Key words:  , Parkinson&rsquo, s disease, microglia, NADPH oxidase, inducible nitric oxide synthase, tyrosine hydroxylase, tanshinone ⅡA, mice

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