摘要
目的探究强化训练通过调节海马蛋白酶体活性对阿尔兹海默症(AD)小鼠认知障碍的影响。方法选取雄性无特定病原级的KM小鼠30只,将其按随机数字表法分为对照组、AD模型组和强化训练组,每组各10只。AD模型组和强化训练组小鼠给予腹腔注射D-半乳糖和苯甲酸钠构建AD模型,对照组无特殊处理。强化训练组在给药后1 h,将其放置于含自由转轮的鼠笼中进行强化训练。实验结束前1周内,通过水迷宫实验、定位航行实验和空间探索实验研究强化训练对AD小鼠的学习记忆和认知能力的影响;通过免疫组织化学实验研究小鼠脑组织切片后DCX、Ki67的阳性表达数和小鼠大脑皮层、海马CAI区内Aβ-42表达情况;通过蛋白酶体活性检测试剂盒检测各组小鼠海马区蛋白酶体活性情况;并利用蛋白质印迹(Western blotting)法检测海马蛋白酶体表达水平。结果与AD模型组相比,强化训练组小鼠的逃避潜伏期延长,在目标象限内的穿越次数和停留时间缩短,且小鼠脑内DCX和Ki67阳性细胞数增多,平均神经元突起的长度也增长(P <0.05),同时大脑皮层和海马CAI区Aβ-42阳性神经元的面积也小于AD模型组,而其海马蛋白酶体活性升高,运动皮层和小脑部位蛋白酶活性也均出现升高的现象(P <0.05);Western blotting结果显示,强化训练后AD小鼠海马区蛋白酶体表达和其亚基PSMB5表达均较AD模型组小鼠表达增强(P <0.05)。结论强化训练可通过调节阿尔兹海默症小鼠海马蛋白酶体活性,降低小鼠Aβ沉积水平,达到增强小鼠学习和记忆能力的目的,改善小鼠的认知功能障碍现象。
Objective To explore the effect of intensive training on cognitive impairment in Alzheimer's mice by regulating hippocampal proteasome activity.Methods Thirty male KM mice with no specific pathogen level were selected and divided into three groups:control group,AD model group and intensive training group according to the random number table method.Mice in the AD model group and the intensive training group were given intraperitoneal injections of D-galactose and sodium benzoate to construct AD models.The control group had no special treatment.Among them,the intensive training group was placed in a squirrel cage with free runners for intensive training 1 hour after the administration.Within 1 week before the end of the experiment,the effects of intensive training on the learning,memory and cognitive ability of AD mice were studied through water maze experiment,positioning navigation experiment and space exploration experiment;the DCX,the number of positive expressions of Ki67 and the expression of Aβ-42 in the mouse cerebral cortex and hippocampal CAI area were detected by immunohistochemistry experiment;the proteasome activity in the hippocampus of each group was detected by the proteasome activity detection kit;and the hippocampal proteasome expression was detected by Western blotting.Results Compared with the AD model group,the mice in the intensive training group had longer escape latency,shorter crossing times and staying time in the target quadrant,and the number of DCX and Ki67 positive cells in the mouse brain increased,and the average neuron protrusion length also increased(P<0.05).At the same time,the area of Aβ-42-positive neurons in the cerebral cortex and hippocampus CAI area was also smaller than that of the AD model group,and the hippocampal proteasome activity increased,and the protease activity of the motor cortex and cerebellum also increased(P<0.05);Western blotting results showed that after intensive training,the expression of proteasome in the hippocampus of AD mice and the expression of its
作者
李润东
孙晓燕
颜亚博
崔秀萍
LI Run-dong;SUN Xiao-yan;YAN Ya-bo(Department of Acupuncture and Rehabilitation,Qingdao Haici Medical Group,Qingdao Shandong 266000,China)
出处
《临床和实验医学杂志》
2021年第6期575-579,共5页
Journal of Clinical and Experimental Medicine
基金
山东省医药卫生科技发展计划项目(编号:2016WS0306)。
