大麻二酚对载脂蛋白E基因敲除小鼠空间记忆障碍的调节及作用机制研究  

Regulation and mechanism of cannabidiol on spatial memory impairment in apolipoprotein E gene knockout mice

作　　者：呼延丽[1] 杨瑛 唐仲亮 HU Yanli;YANG Ying;TANG Zhongliang(Department of Pharmacy,Gansu Provincial People's Hospital,Lanzhou,Gansu,730000,China;Department of Pharmacy,the Third People's Hospital of Gansu Province,Lanzhou,Gansu,730000,China)

机构地区：[1]甘肃省人民医院药剂科,甘肃兰州730000 [2]甘肃省第三人民医院药剂科,甘肃兰州730000

出　　处：《甘肃中医药大学学报》2024年第4期8-14,共7页Journal of Gansu University of Chinese Medicine

基　　金：甘肃省科技计划基金资助项目(20JR10RA383)。

摘　　要：目的研究大麻二酚(CBD)对载脂蛋白E(ApoE)基因敲除(ApoE^(-/-))小鼠空间记忆障碍的调节作用及其作用机制。方法将18只ApoE^(-/-)小鼠采用随机数字表法分为ApoE^(-/-)组和ApoE^(-/-)+CBD组,每组9只。ApoE^(-/-)+CBD组小鼠每天予CBD 10 mg/kg腹腔注射,ApoE^(-/-)组小鼠腹腔注射等量生理盐水,连续注射21 d。最后一次注射后,通过旷场实验和新物体识别实验研究CBD对ApoE^(-/-)小鼠学习记忆能力和焦虑情绪的影响;采用免疫印迹法检测小鼠大脑皮层和海马组织中相关蛋白的表达;培养原代神经元,分为野生型(WT)组、WT+CBD组、ApoE^(-/-)组、ApoE^(-/-)+CBD组4组,观察各组神经元的分化情况。结果ApoE^(-/-)+CBD组小鼠的新物体识别指数明显高于ApoE^(-/-)组,差异有统计学意义(P<0.05)。与WT组比较,ApoE^(-/-)组神经元轴突长度和胞体大小明显缩小,差异均有统计学意义(P<0.01);与ApoE^(-/-)组比较,ApoE^(-/-)+CBD组神经元轴突长度和胞体大小均明显增大,差异均有统计学意义(P<0.05)。与ApoE^(-/-)组比较,ApoE^(-/-)+CBD组小鼠大脑皮层中瞬时受体电位阳离子通道亚家族V成员2(TRPV2)蛋白、磷酸化蛋白激酶B(AKT)及磷酸化钙/钙调蛋白依赖性蛋白激酶Ⅱ型亚基α和δ(CaMKIIα/δ)表达水平明显升高,差异均有统计学意义(P<0.05)。结论CBD可抑制ApoE基因敲除小鼠的空间记忆障碍,减弱ApoE基因敲除小鼠大脑神经元分化障碍,这些作用主要是通过TRPV2/AKT/CaMKIIα/δ通路实现的。Objective To explore the regulating effect of cannabidiol(CBD)on spatial memory impairment in apolipoprotein E gene knockout(ApoE^(-/-))mice and its underlying mechanism.Methods 18 ApoE^(-/-)mice were randomly divided into the ApoE^(-/-)group and the ApoE^(-/-)+CBD group using the random number table method,with 9 mice in each group.Mice in the ApoE^(-/-)+CBD group were intraperitoneally injected with 10 mg/kg of CBD daily,while mice in the ApoE^(-/-)group were intraperitoneally injected with the same volume of normal saline for 21 consecutive days.After the final injection,the effects of CBD on the learning and memory ability as well as anxiety of ApoE^(-/-)mice were investigated through the open field experiment and the new object recognition experiment.The expression of related proteins in the cerebral cortex and hippocampus was detected by Western blotting.Primary neurons were cultured and divided into the wild type(WT),WT+CBD,ApoE^(-/-)and ApoE^(-/-)+CBD groups,and the differentiation of neurons in each group was observed.Results The new object recognition index of the ApoE^(-/-)+CBD group was significantly higher than that of the ApoE^(-/-)group,and the difference was statistically significant(P<0.05).Compared with the WT group,the axon length and cell size of neurons in the ApoE^(-/-)group were significantly reduced,and the difference was statistically significant(P<0.01).Compared with the ApoE^(-/-)group,the axon length and cell size of neurons in the ApoE^(-/-)+CBD group were significantly increased,and the difference was statistically significant(P<0.05).Compared with the ApoE^(-/-)group,the expression levels of transient receptor potential cation channel subfamily V member 2(TRPV2)protein,phosphorylated protein kinase B(AKT),and phosphorylated calcium/calmodulin-dependent protein kinase type II subunitsαandδ(CaMKIIα/δ)in the cerebral cortex of mice in the ApoE^(-/-)+CBD group were significantly elevated.The differences were statistically significant(P<0.05).Conclusion CBD can alleviate spatial memo

关 键 词：空间记忆障碍 载脂蛋白E基因 大麻二酚 旷场实验 新物体识别实验 神经元分化 瞬时受体电位阳离子通道亚家族V成员2 小鼠 实验研究 

分 类 号：R285.5[医药卫生—中药学]