琐琐葡萄黄酮对APP/PS-1双转基因AD小鼠的作用研究

Effect of Flavones from Vitis vinifera L.on APP/PS-1 Double Transgenic AD Mice

目的 探讨琐琐葡萄黄酮(flavones from Vitis vinifera L.,VTF)对APP/PS-1双转基因AD小鼠神经保护作用研究。方法 选用6月龄雄性APP/PS-1双转基因AD小鼠75只,随机分为模型组、阳性对照组(多奈哌齐组,0.7mg/kg)和琐琐葡萄总黄酮(VTF)低、中、高剂量组(70、210、420mg/kg),另取15只同龄雄性C57BL/6小鼠为空白对照组,模型组和空白对照组给予等量0.5%CMC-Na灌胃,8周后采用Morris水迷宫观察小鼠空间认知能力,应用HE染色和免疫组化学染色(IHC)观察小鼠海马CA1区神经元细胞形态以及APP和Aβ_(1~42)蛋白表达情况。结果 与空白对照组比较,模型组小鼠逃逸潜伏期显著延长(P<0.01),有效区域进入次数显著减少(P<0.01);与模型组比较,VTF各剂量组逃逸潜伏期显著缩短(P<0.05),VTF低和中剂量有效区域进入次数显著增多(P<0.05)。镜下观察结果显示,与空白对照组比较,模型组存在大量呈凋亡趋势的神经元细胞,排列不规则,胞质萎缩出现间隙,CA1区APP和Aβ_(1~42)蛋白表达量增加;阳性对照组及VTF各剂量组海马神经元大多数较正常,排列较规整紧密,核仁清晰,核固缩浓染减轻,APP和Aβ_(1~42)蛋白表达量减少。结论 VTF可改善APP/PS-1双转基因AD小鼠学习记忆能力,对小鼠大脑神经元细胞有良好的保护作用,可减少APP和Aβ_(1~42)在小鼠脑内的过表达,对APP/PS-1双转基因AD小鼠具有较好的防治作用。

Objective To investigate the neuroprotective effect of flavones from Vitis vinifera L(VTF) on APP/PS-1 double transgenic AD mice.Methods 75 6-month-old male APP/PS-1 double transgenic AD mice were randomly divided into model group,positive control group(donepezil group,0.7 mg/kg),VTF low,medium,and high-dose groups(70,210,420 mg/kg),another 15 male C57 BL/6 mice of the same age were taken as the blank control group.The model group was given 0.5% CMC-Na,and the blank control group was also given.8 weeks later,the Morris water maze was used to observe the spatial cognitive ability of the mice.HE staining andimmunohistochemical staining(IHC) were used to observe the morphology of neurons in the CA1 area of the mouse hippocampus and the expression of APP and Aβ_(1-42) proteins.Results Compared with the blank control group,the escape latency of mice in the model group was significantly prolonged(P<0.01),and the number of entry into the effective area was significantly reduced(P<0.01).Compared with the model group,the escape latency of each dose group of VTF Significantly shortened(P<0.05),and the number of entry into effective areas of low and medium doses of VTF increased significantly(P<0.05).Microscopic observation showed that compared with the blank control group,the model group had a large number of neuronal cells with apoptotic tendency,with irregular arrangement,gaps in cytoplasmic atrophy,and increased expression of APP and Aβ_(1-42) protein in CA1 area.Most of the hippocampal neurons in the positive control group and the VTF dose groups were relatively normal,arranged relatively tightly,with clear nucleoli,reduced nucleus pyknosis and decreased expression of APP and Aβ_(1-42) protein.Conclusion VTF can improve the learning and memory ability of APP/PS-1 double transgenic AD mice,and has a better protective effect on mouse brain neurons.It can reduce the overexpression of APP and Aβ_(1-42) in the mouse brain.VTF has a good preventive effect on APP/PS-1 double transgenic AD mice.