神经血管单元体外模型在川陈皮素抗阿尔茨海默病作用中的应用

Application of NVU model in nobiletin anti-Alzheimer’s disease

目的观察神经血管单元(neurovascular unit,NVU)联合细胞模型与神经元单独培养在评价川陈皮素(nobiletin,NOB)体外抗阿尔茨海默病(Alzheimer disease,AD)活性的差异。方法建立NVU联合细胞培养方法,用MTT法比较NOB对Aβ1-42诱导NVU及单一神经元培养模型中神经元损伤的影响,采用回避实验及新物体识别实验观察NOB对Aβ1-42侧脑室注射拟AD模型小鼠行为学的影响。结果动物实验结果表明,NOB在25 mg/kg、50 mg/kg剂量下可改善AD模型小鼠的学习记忆障碍,延长回避潜伏期,减少错误次数,提高新物体分辨指数(P值均<0.05);在NVU联合细胞培养中,25 mg/kg、50 mg/kg剂量的NOB可使神经元的存活率由62.64%分别提高至79.68%、90.83%,提示NOB具有神经保护作用(P<0.05),而在单一神经元培养中,NOB使神经元存活率由65.25%分别提高至67.46%、72.16%,未显示其神经元保护作用(P>0.05)。结论NVU联合细胞培养更适用于NOB的作用机制研究。

Objective To observe the difference between neurovascular unit(NVU)combined cell model and neuron culture alone in evaluating anti-Alzheimer disease(AD)activity of nobiletin(NOB).Methods The effect of NOB on neuron injury induced by Aβ1-42 in NVU and single neuron culture model was compared by MTT method.The effects of NOB on the behavior of Aβ1-42-induced AD mice were observed by avoidance test and new object recognition test.Results The animal experiments showed that NOB at 25 mg/kg and 50 mg/kg improves the learning and memory impairment,prolongs the avoidance latency,reduces the number of errors,and improves the resolution index of new objects(P<0.05).In the combined cell culture of NVU,the survival rate of neurons increased from 62.64%to 79.68%and 90.83%with the dosage of 25 mg/kg and 50 mg/kg,suggesting that NOB has neuroprotective effect(P<0.05),while in the single cell culture,the survival rate of neurons increased from 65.25%to 67.46%and 72.16%with no neuroprotective effect(P>0.05).Conclusion NVU combined cell culture is more suitable for the study of the mechanism of NOB.