基于玄府气血理论研究风药组方对血管性痴呆大鼠海马突触兴奋性氨基酸受体的影响

Effect of Wind Drugs Decotion on Hippocampal Synaptic Excitatory Amino Acid Receptors of Rats with Vascular Dementia Based on Xuanfu Qi and Blood Theory

目的:探讨风药组方血管性痴呆(VaD)大鼠海马突触兴奋性氨基酸受体的影响。方法:SD大鼠随机法分为假手术组、模型组、西药对照组(6.25mg/kg尼莫地平)和通窍益智颗粒24.8g/kg组、12.4g/kg组、6.2g/kg组,永久性闭塞双侧颈总动脉(2-VO)法建立VaD模型。术后连续灌胃30d,然后进行行为学评价,免疫组化检测BDNF阳性表达,Western Blot检测pCREB和NMDA受体亚基GluN1、GluN2B及AMPA受体亚基GluA2的表达。结果:与模型组相比,西药对照组和通窍益智颗粒各剂量组大鼠学习记忆能力显著提高,BDNF表达增加,pCREB、GluN1、GluN2B和GluA2表达明显上调(P<0.05),且通窍益智颗粒24.8g/kg组效果显著高于其他各组(P<0.05)。结论:基于开通玄府法重用风药组方,可改善血管性痴呆大鼠的学习记忆能力,其机制与提高海马神经元内pCREB表达,介导上调BDNF及突触后膜兴奋性氨基酸受体亚基蛋白水平从而调控突触可塑性相关。

Objective:To investigate the effects of vascular dementia(VaD)on excitatory amino acid receptors in hippocampal synapses in rats.Methods:60 rats were randomLy divided into sham operation group,model group,positive control group and 24.2,12.4 and 6.5 dose of TQYZKL of wind drugs decotion groups.The model of vascular dementia was established by permanent ligation of bilateral common carotid arteries(2-VO).The behavioral changes of rats were evaluated by Morris water maze,the expression of BDNF was detected by immunohistochemistry,and the expression of pCREB,NMDA receptor subunit GluN1,GluN2 Band AMPA receptor subunit GluA2 was detected by Western Blot.Results:Compared with the model group,the learning and memory ability was significantly improved,the positive area of BDNF was increased,and the expression of pCREB,GluN1,GluN2 Band GluA2 was up-regulated in the positive control group and each dose group of traditional Chinese medicine.The effect of 24.2 dose of TQYZKL was significantly higher than that of other groups.Conclusion:based on the ideology of Opening Xuanfu,decotion valueing wind drugs can improve the ability of learning and memory in rats with vascular dementia,and its mechanism may be related to enhencing the expression of pCREB in hippocampal neurons,thus mediating the up-regulation of BDNF and the level of excitatory amino acid receptor subunits in postsynaptic membrane to regulate synaptic plasticity.