Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Oct 25;50(5):553-560. doi: 10.3724/zdxbyxb-2021-0056.
To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.
探讨依达拉奉对阿尔茨海默病(AD)模型小鼠行为学及血脑屏障(BBB)的影响。
将 38 只 4 月龄 APP/PS1 双转基因 AD 小鼠随机分为模型组、低剂量组、高剂量组,每组 13 只。分别给予生理盐水和 12、24 g·kg·d 依达拉奉灌胃 1 次/d,连续给药 6 周。采用旷场实验和条件恐惧实验检测各组小鼠的日常活动和恐惧条件记忆行为的变化,采用硫黄素 T 染色检测各组小鼠皮质和海马 CA1 区β-淀粉样蛋白(Aβ)沉积,采用 CD34 与纤维蛋白原(Fib)免疫荧光双标染色检测各组小鼠血管内皮完整性及 BBB 渗出情况。
与模型组比较,低、高剂量组小鼠的日常活动明显改善(均<0.01),高剂量组小鼠的恐惧记忆能力明显增强(<0.01);高剂量组小鼠皮质和海马 CA1 区 Aβ沉积量显著减少,面积比显著降低(均<0.05);低剂量组小鼠海马 CA1 区 Aβ沉积量的面积比也降低(<0.05)。低、高剂量组小鼠皮质 CD34 阳性面积比例增加,Fib 阳性面积比例降低(均<0.05);高剂量组小鼠海马 CA1 区 CD34 阳性面积比例显著增加,Fib 阳性面积比例显著降低(均<0.05)。
依达拉奉能改善 APP/PS1 小鼠的日常活动和恐惧条件记忆功能,减少脑内 Aβ的沉积,其机制可能与降低 BBB 通透性、保护 BBB 完整性有关。