正五聚蛋白-3对5×FAD小鼠的记忆改善作用及Aβ表达的影响

Effect of pentraxin-3 on memory improvement and Aβexpression in 5×FAD mice

目的探讨正五聚蛋白-3(PTX3)对阿尔茨海默病(AD)模型小鼠的记忆改善作用及β-淀粉样蛋白(Aβ)浓度的影响。方法(1)5月龄5×FAD小鼠10只,按随机数字表法分为模型组和PTX3干预组,每组5只,另取C57BL/6野生型小鼠5只作为正常对照组。PTX3干预组小鼠立体定位注射0.5 g/L PTX3溶液4μL,模型组和正常对照组小鼠注射等量PBS。采用Y迷宫实验检测3组小鼠的短期记忆力,采用Morris水迷宫实验检测3组小鼠的学习记忆能力,采用ELISA实验检测3组小鼠大脑半球Aβ_(40)和Aβ_(42)的浓度。(2)3月龄5×FAD小鼠25只,按随机数字表法分为模型组、2μg/kg PTX3干预组、4μg/kg PTX3干预组、8μg/kg PTX3干预组、16μg/kg PTX3干预组,每组5只,分别鼻腔内注射20μL PBS,2μg/kg、4μg/kg、8μg/kg、16μg/kg PTX3溶液,另取C57BL/6野生型小鼠5只作为正常对照组,鼻腔内注射等量PBS,每96小时给药1次,共给药7次。采用Y迷宫实验检测6组小鼠的短期记忆力,采用Morris水迷宫实验检测6组小鼠的学习记忆能力,采用ELISA实验检测6组小鼠海马Aβ_(40)和Aβ_(42)的浓度。结果(1)与模型组比较,PTX3干预组小鼠的逃避潜伏期较短、平台象限时间百分比较高,自主交替百分比较高,差异有统计学意义(P<0.05)。与模型组[(63.38±21.42)pg/mL、(29.77±6.11)pg/mL]比较,PTX3干预组小鼠大脑半球中Aβ_(40)和Aβ_(42)浓度[(15.87±2.11)pg/mL、(16.55±1.95)pg/mL]较低,差异均有统计学意义(P<0.05)。(2)与模型组比较,16μg/kg PTX3干预组小鼠的逃避潜伏期较短、平台象限时间百分比较高,差异均有统计学意义(P<0.05)。与模型组比较,2μg/kg PTX3干预组和16μg/kg PTX3干预组小鼠的自主交替百分比较高,差异均有统计学意义(P<0.05)。与模型组比较,8μg/kg、16μg/kg PTX3干预组小鼠海马中Aβ_(40)、Aβ_(42)浓度较低,差异均有统计学意义(P<0.05)。结论PTX3对5×FAD小鼠的记忆有明显改善作用,且能有效降低小鼠脑内Aβ的浓度。

Objective To explore the effect of pentraxin 3(PTX3)on memory improvement and Aβexpression in Alzheimer's disease(AD)model mice.Methods(1)Ten 5-month-old 5×FAD mice were randomly divided into PTX3 group and model group(n=5);5 C57BL/6 wild-type mice at the same age were selected as control group;mice in the PTX3 group and control group were stereotactically injected 4μL 0.5 g/L PTX3 or same dose of phosphate buffered saline(PBS);Morris water maze test was used to detect the learning and memory abilities,Y maze test was used to detect the short-term memory,and ELISA was used to obsevre the contents of Aβ_(40) and Aβ_(42) in the brain hemisphere.(2)Twenty-five 3-month-old 5×FAD mice were randomly divided into model group,2μg/kg PTX3 group,4μg/kg PTX3 group,8μg/kg PTX3 group,and 16μg/kg PTX3 group(n=5);5 C57BL/6 wild-type mice at the same age were selected as control group;mice in the PTX3 groups were intranasally injected 2,4,8,and 16μg/kg PTX3,respectively;those in the model group and control group were intranasally injected same dose of PBS;injection was given once every 96 h for a total of 7 times.Morris water maze test was used to detect the learning and memory abilities,Y maze test was used to detect the short-term memory,and ELISA was used to obsevre the contents of Aβ_(40) and Aβ_(42) in the hippocampus.Results(1)Compared with the model group,the PTX3 group had significantly shorter platform latency,higher percentage of exploration time and higher percentage of spontaneous alternations(P<0.05).Compared with those in model group([63.38±21.42]pg/mL,[29.77±6.11]pg/mL),the concentrations of Aβ_(40) and Aβ_(42) in the brain tissues of PTX3 group([15.87±2.11]pg/mL,[16.55±1.95]pg/mL)were statistically lower(P<0.05).(2)Compared with the model group,the 16μg/kg PTX3 group had significantly shorter escape latency and higher percentage of exploration time(P<0.05);compared with the model group,the 2μg/kg PTX3 group and 16μg/kg PTX3 group had significantly higher percentage of spontaneous alternations(P<0.05).The contents of Aβ_(40) and Aβ_(42) in the hippocampus of 8μg/kg PTX3 group and 16μg/kg PTX3 group were statistically lower compared with those in the model group(P<0.05).Conclusion PTX3 may attenuate cognitive deficits and decrease Aβexpression in the brain or hippocampus tissues of 5×FAD mice with AD.