长春西汀对脑缺血保护作用

Protective Effect of Vinpocetineon Cerebral Ischemia

目的观察长春西汀对大鼠纹状体神经末梢多巴胺(DA)及其主要代谢产物3,4-二羟基苯乙酸(DOPAC)的影响,了解长春西汀对脑缺血的保护机制。方法 10只雄性Wistar大鼠的纹状体。通过内源性儿茶酚胺释放实验观察DA和DOPAC的基础释放水平,通过加载[3H]DA释放实验观察藜芦定(对照)或含1.5,5,15,50μmol·L^(-1)长春西汀对DA和DOPAC释放的影响。结果长春西汀不会改变内源DA的基础释放水平,但影响藜芦定诱发DA的释放。与对照组(10±1)pmol·mg^(-1)比较,藜芦定去极化引起DA显著提高到(122±10)pmol·mg^(-1)。长春西汀处理后,藜芦定诱导的DA释放降到(18±1)pmol·mg^(-1),随着长春西汀浓度升高(1.5,5,15,50μmol·L^(-1)),内部DA浓度逐渐降低,而DOPAC释放增加,但DA的基础释放水平不变,内部DOPAC浓度不变。比较不同浓度长春西汀处理后突触体内总DA和总DOPAC,发现DA损失和DOPAC形成之间存在剂量依赖的相关性。结论通过突触前神经细胞电压敏感性钠离子通道(VSSC)通透性提高引起神经递质释放的抑制作用是长春西汀神经保护作用的机制之一,长春西汀不仅能选择性抑制多巴胺转运体介导的DA释放,同时能通过VSSC非依赖的机制提高DOPAC的合成。

Objective To investigate the influence of vinpocetine on release of corpus striatum nerve terminal dopamine （DA） and its main metabolite 3,4-dihydroxyphenylacetic acid （DOPAC）,and to understand the mechanism underlying protective effect of vinpocetine on cerebral ischemia on rats. Methods Corpus striatumof of ten male Wistar rats was harvested.Baseline release levels of DA and DOPAC were determined by endogenous catecholamine release test.Influence of veratridine （control） and vinpocetine （1.5,5,15 and 50 μmol·L^-1） on release of DA and DOPAC was tested through[^3H]DA release test. Results Fluoxetine did not change the base line release of endogenous DA,but influenced the veratridine-evoked release of DA.Veratridine depolarization significantly increased DA release as compared with the control group[（122 ±10） pmol·mg^-1 vs. （10±1） pmol·mg^-1].After treatment vinpocetine,veratridine-induced DA release was reduced to （18±1） pmol·mg^-1,along with the increasing concentration of vinpocetine （1.5,5,15,50 μmol·L^-1）,internal DA concentration decreased,but DOPAC release increased,the baseline DA release level was unchanged,and the internal DOPAC concentration was constant.After treated with different concentration of vinpocetine,total DA and DOPAC in synapsis was compared and a dose-dependent relationship was found between DA loss and DOPAC formation. Conclusion Release of neurotransmitters is inhibited through increasing permeability of voltage sensitive Na channels （VSSC） of presynaptic nerve cells,which is one of the mechanisms underlying neuro protective effect of vinpocetine.Vinpocetine can not only selectively inhibit DA transporter-induced DA release,but also increase synthesis of DOPAC independent of VSSC.