楮实子提取物对APP/PS1小鼠学习记忆能力及对PI3K-CREB-XBP1信号通路的影响

Effect of extract of fructus broussonetiae on learning and memory impairment in APP/PS1 mice and its effect on PI3K-CREB-XBP1 signaling pathway

目的:探讨楮实子提取物对APP/PS1小鼠学习记忆能力的改善作用及其作用机制。方法:将7月龄的APP/PS1小鼠随机分为模型组、楮实子低剂量组(2 g/kg)、楮实子高剂量组(4 g/kg)和阳性药组(10 mg/kg盐酸多奈哌齐),同龄C57BL/6小鼠作为对照组,每组10只,连续治疗8周。Morris水迷宫观察各组小鼠认知功能改善情况;免疫荧光染色检测各组小鼠海马区星形胶质细胞、小胶质细胞活化情况;免疫荧光染色及Western blot检测Aβ1-42沉积情况;Western blot检测BACE1、ADAM10蛋白表达及PI3K-CREB-XBP1信号通路PI3K、p-PI3K、CREB、p-CREB、XBP1s及XBP1u蛋白表达情况。结果:楮实子低、高剂量组及阳性药组小鼠的学习与记忆能力均有所提高,小鼠逃避潜伏期明显缩短,目标象限停留时间延长,穿越平台次数增加;GFAP及Iba-1阳性细胞数量明显降低;Aβ1-42沉积也显著减少;ADAM10蛋白表达增加,而BACE1蛋白表达降低;p-PI3K/PI3K、p-CREB/CREB及XBP1s/XBP1u显著增加,与模型组相比,差异具有统计学意义(P<0.05)。结论:楮实子提取物能够抑制APP/PS1小鼠Aβ1-42沉积,改善其学习记忆能力,可能与激活PI3K-CREB-XBP1信号通路有关。

Objective:To investigate the effect of the extract of fructus broussonetiae(FB) on the learning and memory ability of APP/PS1 mice and its might mechanism.Methods:7-month old APP/PS1 mice were randomly divide into the model group,the FB low dose group(FB-L,2 g/kg),high dose group(FB-H,4 g/kg),and donepezil hydrochloride group(DH,10 mg/kg),age-matched C57 BL/6 mice as the control group,10 mice in each group,continuous intragastric administration for 8 weeks.The Morris water maze was used to observe the improvement of cognitive function in each group.Immunofluorescence staining was used to detect the activation of astrocytes and microglia in hippocampus of each group.Immunofluorescence staining and Western blot was used to detect the deposition of Aβ1-42;Western blot was used to detect the expression of BACE1,ADAM10 protein and PI3 K-CREB-XBP1 signaling pathway-related proteins PI3 K,p-PI3 K,CREB,p-CREB,XBP1 s and XBP1 u.Results:In the FB-L,FB-H and DH groups,the learning and memory abilities of mice were improved,the escape latency of mice was significantly shortened,the target quadrant staying time was prolonged,and the number of crossing platforms increased.The number of GFAP and Iba-1 positive cells was significantly decreased;Aβ1-42 deposition was also significantly reduced;ADAM10 protein expression was increased,while BACE1 protein expression was decreased;p-PI3 K/PI3 K,p-CREB/CREB and XBP1 s/XBP1 u were significantly increased,compared with the model group,the difference was statistically significant(P<0.05).Conclusion:The extract of fructus broussonetiae could inhibit the deposition of Aβ1-42 in APP/PS1 mice and improve its learning and memory ability,which may be related to the activation of PI3 K-CREB-XBP1 signaling pathway.