血管活性肠肽抑制帕金森病MPTP模型小鼠纹状体中核因子-κB p65、肿瘤坏死因子α和单核细胞趋化蛋白-1的上调

摘要

Objective:To investigate the effect of vasoactive intestinal peptide (VIP) on the neuroinflammation and the protein level of nuclear factor-κB p65 (NF-κB p65) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD).Methods:Thirty male C57BL/6J mice were randomly divided into normal saline (NS) group,MPTP group and MPTP+VIP.Immunohistochemistry was used to observe the level of tyrosine hydroxylase (TH),glial cell fibrous acid protein (GFAP) and ion-calcium-binding protein (Iba-1).The contents of tumor necrosis factor alpha (TNFα) and monocyte chemotactic protein 1 (MCP-1) in the striatum were detected by ELISA.The level of NF-κB p65 was measured by Western blotting.Results:Compared with NS group,the level of TH was significantly decreased,the level of GFAP and Iba-1 was obviously elevated,and the contents of TNF-α,MCP-1 and the level of NF-κB p65 in the striatum of MPTP group were significantly increased.However,VIP sufficiently ameliorated TH depletion in the striatum of the MPTP-induced mice,and evidently suppressed the activation of microglia and astrogliosis.In addition,VIP inhibited the abnormal elevation of the content of TNFα and MCP-1,and restrained the level of NF-κB p65 in the striatum of MPTP-induced mice.Conclusion:VIP can effectively reverse the neurological damage of the striatum in the MPTP-induced mice by down-regulating the level of NF-κB p65.%目的:研究血管活性肠肽(VIP)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠纹状体神经炎症及核因子-κB p65(NF-κB p65)水平的影响.方法:C57BL/6J雄性小鼠30只随机分为生理盐水(NS)组、MPTP组、MPTP+ VIP组.免疫组织化学法观察纹状体酪氨酸羟化酶(TH)、胶质纤维酸性蛋白(GFAP)和离子钙结合蛋白(Iba-1)的水平变化;ELISA法检测肿瘤坏死因子α(TNF-α)及单核细胞趋化蛋白-1(MCP-1)的含量;免疫印迹检测NF-κB p65的水平变化.结果:与NS组相比,MPTP组小鼠纹状体TH水平显著减少,GFAP和Iba-1水平显著上升,TNFα和MCP-1的含量及NF-κB p65的水平显著升高.给予VIP后,纹状体TH水平明显增加,GFAP和Iba-1水平显著下降,TNF-和MCP-1的含量及NF-κB p65的水平明显降低.结论:VIP可能通过降低NF-κB p65的水平从而抑制MPTP诱导的PD小鼠纹状体的神经炎症反应.