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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons.
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Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons.

机译：长春西汀对原代皮层神经元线粒体功能和神经保护的影响。

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摘要

Vinpocetine (ethyl apovincaminate), a synthetic derivative of the Vinca minor alkaloid vincamine, is widely used for the treatment of cerebrovascular-related diseases. One of the proposed mechanisms underlying its action is to protect against the cytotoxic effects of glutamate overexposure. Glutamate excitotoxicity leads to the disregulation of mitochondrial function and neuronal metabolism. As Vinpocetine has a binding affinity to the peripheral-type benzodiazepine receptor (PBR) involved in the mitochondrial transition pore complex, we investigated whether neuroprotection can be at least partially due to Vinpocetine's effects on PBRs. Neuroprotective effects of PK11195 and Ro5-4864, two drugs with selective and high affinity to PBR, were compared to Vinpocetine in glutamate excitotoxicity assays on primary cortical neuronal cultures. Vinpocetine exerted a neuroprotective action in a 1-50microM concentration range while PK11195 and Ro5-4864 were only slightly neuroprotective, especially in high (>25microM) concentrations. Combined pretreatment of neuronal cultures with Vinpocetine and PK11195 or Ro5-4864 showed increased neuroprotection in a dose-dependent manner, indicating that the different drugs may have different targets. To test this hypothesis, mitochondrial membrane potential (MMP) of cultured neurons was measured by flow cytometry. 25microM Vinpocetine reduced the decrease of mitochondrial inner membrane potential induced by glutamate exposure, but Ro5-4864 in itself was found to be more potent to block glutamate-evoked changes in MMP. Combination of Ro5-4864 and Vinpocetine treatment was found to be even more effective. In summary, the present results indicate that the neuroprotective action of vinpocetine in culture can not be explained by its effect on neuronal PBRs alone and that additional drug targets are involved.
机译：长春西汀（长春西汀乙酯）是长春蔓小生物碱长春胺的合成衍生物，被广泛用于治疗与脑血管相关的疾病。其作用基础的拟议机制之一是防止谷氨酸过度暴露的细胞毒性作用。谷氨酸兴奋性毒性导致线粒体功能和神经元代谢失调。由于长春西汀与参与线粒体过渡孔复合体的外周型苯并二氮杂receptor受体（PBR）具有结合亲和力，因此我们研究了神经保护作用是否至少部分归因于长春西汀对PBR的影响。在原代皮层神经元培养物的谷氨酸兴奋性毒性试验中，将两种对PBR具有选择性和高度亲和力的药物PK11195和Ro5-4864的神经保护作用与长春西汀进行了比较。长春西汀在1-50microM的浓度范围内发挥神经保护作用，而PK11195和Ro5-4864仅对神经有轻微保护作用，尤其是在高浓度（> 25microM）下。用长春西汀和PK11195或Ro5-4864对神经元培养物进行联合预处理显示出剂量依赖性的神经保护作用增强，表明不同的药物可能具有不同的靶标。为了检验该假设，通过流式细胞仪测量了培养的神经元的线粒体膜电位（MMP）。 25microM长春西汀减少了谷氨酸暴露引起的线粒体内膜电位的降低，但发现Ro5-4864本身更有效地阻止了谷氨酸引起的MMP变化。发现Ro5-4864和长春西汀联合治疗更为有效。总之，本结果表明长春西汀在培养物中的神经保护作用不能通过其对单独的神经元PBR的作用来解释，并且涉及其他药物靶标。

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