电针对AD大鼠学习记忆能力及额叶皮质SIRT1/FOXO3a表达的影响

Effects of Electroacupuncture on Learning-memory Ability and Expressions of SIRT1/FOXO3a in the Frontal Cortex of Alzheimer’s Disease Rats

目的:观察电针对阿尔茨海默症(AD)大鼠额叶皮质沉默信息调节因子2同源蛋白1(SIRT1)和叉头框转录因子O3a(FOXO3a)表达的影响,探讨电针治疗AD的可能机制。方法:将18只雄性SD大鼠随机分为对照组、模型组和电针组,每组6只。模型组和电针组采用链脲佐菌素(STZ)侧脑室注射制作AD大鼠模型,电针组用电针刺激"大椎"穴和"百会"穴,连续治疗14d,30min/次,1次/d。通过Morris水迷宫检测大鼠学习记忆能力的改变,尼氏染色观察各组细胞形态变化,同时通过免疫组织化学方法检测各组额叶皮质SIRT1和FOXO3a的表达情况。结果:(1)Morris水迷宫:与对照组相比,模型组平均逃避潜伏期延长(P<0.05),平台象限滞留时间百分比降低(P<0.05);与模型组相比,电针组平均逃避潜伏期降低(P<0.05),平台象限滞留时间百分比提高(P<0.05)。(2)尼氏染色:模型组额叶皮质神经元层次明显紊乱,细胞增多,部分胞质萎缩;电针组额叶皮质神经元形态接近对照组。(3)免疫组化:在大鼠额叶皮质,与对照组相比,模型组的SIRT1表达明显减弱(P<0.05),FOXO3a表达明显增强(P<0.05);与模型组相比,电针组的SIRT1表达增强(P<0.05),FOXO3a表达减弱(P<0.05)。结论:电针可改善AD大鼠的学习记忆能力,其机制可能与电针通过上调SIRT1的表达和下调FOXO3a的表达,从而抑制额叶皮质内氧化应激反应有关。

Objective:To observe the effects of electroacupuncture(EA)on expressions of silent mating type information regulation 2 homolog 1(SIRT1)and Forkhead box O3 a(FOXO3 a)in Alzheimer’s disease(AD)rats,so as to explore its possible mechanism underlying treatment of AD rats.Methods:18 SD male rats were randomly divided into control group,model group and EA group,6 each.The AD model was made by streptozotocin(STZ)injected into the bilateral ventricle,EA group(2 V,2 Hz)was performed on"dazhui"and"baihui"for 30 minutes,once daily for successively 14 days.Morris water maze tests were used to evaluate the rat’s learning-memory ability,nissl staining was use to observe the morphological change of neurons in the frontal cortex region,meanwhile,the expressions of SIRT1 and FOXO3 a in the frontal cortex region was measured by immunohistochemical staining.Results:(1)Morris water maze tests showed that:compared with the control group,the escape latency was obviously prolonged(P<0.05),and the percentage of platform quadrant residence duration was considerably lowered in the model group(P<0.05);after the treatment,compared with the model group,the escape latency was significantly shortened(P<0.05),and the percentage of platform quadrant residence duration was definitely increased in EA group(P<0.05).(2)Nissl staining showed that:the number of neurons in the frontal cortex region were increased and arrangement was obviously disordered in the model group,part of cytoplasm was atrophied at the same time.In EA group,the morphology of neurons was similar to the control group.(3)Immunohistochemical staining showed that:in the frontal cortex region of rat,compared with the control group,the expression levels of SIRT1 was significantly reduced(P<0.05),and FOXO3 a’expression levels was noticeably heightened in model group(P<0.05);after the treatment,compared with the model group the expression levels of SIRT1 was significantly increased(P<0.05),and FOXO3 a’expression levels was noticeably decreased in EA group(P<0.05).Conclusion:Electroacupuncture can improve the learning-memory ability in AD rats,which mechanism may be connected with the expression levels of SIRT1 up-regulated and the expression levels of FOXO3 a down-regulated,and then restrained oxidative stress in the frontal cortex region.