辛伐他汀对APP/PS1小鼠学习记忆能力及对NLRP3炎症小体的影响  

Effect of simvastatin on learning and memory ability and NLRP3 inflammasome in APP/PS1 mice

作　　者：徐巍[1] 王丽霞[1] 刘欣[1] 梁勇[1] 林春花[1] XU Wei;WANG Li-xia;LIU Xin;LIANG Yong;LIN Chun-hua(Department of Neurology,Tieling Central Hospital,Tieling 112001,China)

机构地区：[1]铁岭市中心医院神经内科,辽宁铁岭112001

出　　处：《解剖科学进展》2020年第5期555-558,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180551091)。

摘　　要：目的探究辛伐他汀对APP/PS1转基因小鼠学习记忆能力的影响及其与NLRP3炎症小体的关系。方法7月龄APP/PS1小鼠20只,随机分为阿尔茨海默模型组(APP)、辛伐他汀治疗组(Sim),每组10只;另取同龄SPF级C57BL/6小鼠作为对照组(control);辛伐他汀治疗组予以辛伐他汀灌胃治疗。HE染色检测小鼠海马组织结构;TUNEL检测小鼠海马区神经细胞凋亡情况;免疫荧光染色检测小鼠海马区GFAP及Iba-1的表达;Morris水迷宫检测各组小鼠的学习与记忆能力;Western blot检测小鼠海马区IL-1、Caspase-1、IL-18及NLRP3蛋白的表达。结果辛伐他汀改善了APP/PS1小鼠海马DG区神经细胞结构,降低了神经细胞凋亡数量(P<0.05),并且降低了GFAP及Iba-1阳性细胞数量(P<0.05);辛伐他汀还缩短了小鼠逃避潜伏期,延长单位时间内目标象限停留时间,增加穿台次数(P<0.05);辛伐他汀还能够抑制IL-1、Caspase-1、IL-18及NLRP3蛋白的表达(P<0.05)。结论辛伐他汀改善APP/PS1小鼠学习记忆能力,与抑制海马区神经细胞凋亡和胶质细胞活化,抑制NLRP3炎症小体的激活相关。Objective To explore the effect of simvastatin on learning and memory ability of APP/PS1 transgenic mice and its relationship with NLRP3 inflammasome.Methods Twenty 7-month-old APP/PS1 mice were randomly divided into the alzheimer’s model group(APP)and simvastatin treatment group(Sim)with 10 mice in each group.In addition,SPF C57 BL/6 mice of the same age were taken as the control group,and the simvastatin treatment group was treated with simvastatin gavage.The hippocampal structure of mice was detected by HE staining.TUNEL was used to detect the apoptosis of nerve cells in the hippocampus of mice.The expression of GFAP and Iba-1 in the hippocampus of mice was detected by immunofluorescence staining.Morris water maze was used to test the learning and memory abilities of each group.The expressions of IL-1,Caspase-1,IL-18 and NLRP3 in the hippocampus of mice were detected by Western blot.Results Simvastatin improved the structure of nerve cells in the hippocampal DG region of APP/PS1 mice,reduced the number of neuronal apoptosis(P<0.05),and decreased the number of GFAP and Iba-1 positive cells(P<0.05);It also shortened the escape latency of mice,prolonged the target quadrant residence time per unit time,and increased the number of passes(P<0.05).Simvastatin also inhibited the expression of IL-1,Caspase-1,IL-18 and NLRP3 proteins.(P<0.05).Conclusion imvastatin improved the ability of learning and memory,which is related to inhibiting the neuronal apoptosis and activation of glial cells and activation of NLRP3 inflammatory bodies.

关 键 词：辛伐他汀 阿尔茨海默病 学习记忆能力 NLRP3炎症小体 APP/PS1小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学]