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优化 DNA 疫苗的免疫效果及其在帕金森病 MPTP 模型中的保护作用。

Immune effects of optimized DNA vaccine and protective effects in a MPTP model of Parkinson's disease.

机构信息

Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st Youyi Road, Yuzhong District, 400016, Chongqing, China,

出版信息

Neurol Sci. 2013 Sep;34(9):1559-70. doi: 10.1007/s10072-012-1284-6. Epub 2013 Jan 25.

Abstract

It has been suggested that DNA vaccine plays a protective effect on degenerative diseases in the central nervous system (CNS), the Parkinson's disease (PD) included. In this study, we assessed the immune effects of optimized DNA vaccine (pVAX1-IL-4/SYN-B) in the C57BL/6 mice by ELISA, and immunohistochemistry. We also evaluated the neuroprotective effect of pVAX1-IL-4/SYN-B in MPTP model of Parkinson's disease, using behavioral methods, immunohistochemistry and western blot. We found that alphα-synuclein (α-syn) antibody significantly increased, IL-4 increased and IFN-r reduced in the serum of immunized C57BL/6 mice in optimized DNA vaccine group. The immune serum of mice specifically combined with the α-syn positive inclusion bodies in the brain of PD model mice. The preventive immunization with optimized DNA vaccine made the motor symptoms improved significantly, the apoptosis of tyrosine hydroxylase (TH) neuron and cyclooxygenase-2 (COX-2) expression significantly decreased in MPTP model mice. These results suggest that optimized DNA vaccine can make immunized mice produce high titers of specific α-syn antibody, mainly causing the humoral immune response; preventive immunization with optimized DNA vaccine can play neuroprotective and anti-inflammatory effects on mice suffering from the sub-acute MPTP Parkinson's disease.

摘要

有人提出 DNA 疫苗对中枢神经系统(CNS)退行性疾病,包括帕金森病(PD)具有保护作用。在这项研究中,我们通过 ELISA 和免疫组织化学评估了优化 DNA 疫苗(pVAX1-IL-4/SYN-B)在 C57BL/6 小鼠中的免疫效果。我们还使用行为方法、免疫组织化学和 Western blot 评估了 pVAX1-IL-4/SYN-B 在 MPTP 诱导的帕金森病模型中的神经保护作用。结果发现,优化 DNA 疫苗组免疫 C57BL/6 小鼠的血清中α-突触核蛋白(α-syn)抗体显著增加,IL-4 增加,IFN-r 减少。免疫小鼠的血清特异性结合 PD 模型小鼠脑内的α-syn 阳性包涵体。预防性免疫优化 DNA 疫苗使运动症状明显改善,MPTP 模型小鼠的酪氨酸羟化酶(TH)神经元凋亡和环氧化酶-2(COX-2)表达明显减少。这些结果表明,优化 DNA 疫苗可使免疫小鼠产生高水平的特异性α-syn 抗体,主要引起体液免疫反应;预防性免疫优化 DNA 疫苗可对亚急性 MPTP 诱导的帕金森病小鼠发挥神经保护和抗炎作用。

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