IGF-1对睡眠剥夺模型小鼠认知功能的影响及海马IGF-1/PI3K/Akt信号通路的调节作用  

Effect of IGF-1 on cognitive function and the regulation of IGF-1/PI3K/Akt signal pathway in hippocampus of sleep deprived mice

作　　者：高微 吴伟[1] 周凯丽 万亚会 郑培 赵晓楠 薛蓉[1] Gao Wei;Wu Wei;Zhou Kaili;Wan Yahui;Zheng Pei;Zhao Xiaonan;Xue Rong(Neurology Department,Tianjin Medical University General Hospital,Tianjin 300000,China;Neurology Department,Beijing Friendship Hospital Pinggu Hospital,Beijing 101200,China;Neurology Department,Tianjin Medical University General Hospital Airport Site,Tianjin 300308,China;Internal Medicine,Tianjin Children's Hospital,Tianjin 300000,China)

机构地区：[1]天津医科大学总医院神经内科,300000 [2]北京友谊医院平谷医院神经内科,101200 [3]天津医科大学总医院空港医院神经内科,300308 [4]天津市儿童医院内科,300000

出　　处：《中华行为医学与脑科学杂志》2020年第5期419-425,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：天津市科技计划项目(17ZXMFSY00180)。

摘　　要：目的:探讨胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)对睡眠剥夺模型小鼠认知功能的影响和可能的作用机制。方法:将C57BL/6J小鼠(8周龄大小)随机分为4组(每组6只):正常对照组(CC组)、REM期睡眠剥夺5 d组(SD组)、REM期睡眠剥夺5 d+腹腔注射IGF-1组(SD+IGF-1组)、REM期睡眠剥夺5 d+腹腔注射PBS组(SD+PBS组)。采用Morris水迷宫对小鼠进行认知功能测试,利用Elisa法测定小鼠海马组织IGF-1蛋白含量,利用RT-qPCR测定小鼠海马组织TNF-α、IL-1β、IL-6 mRNA表达量;利用Western blot检测各组小鼠海马组织p-Akt、Akt、p-GSK3β、GSK3β、Bcl-2、Caspase-9蛋白表达量。结果:SD组小鼠处于目标象限时间、穿越平台次数[(11.87±1.67)s,(12.50±5.54)次]低于CC组[(19.40±1.75)s,(22.17±8.21)次],差异有统计学意义( t=8.71,2.26,均 P<0.05);SD+IGF-1组小鼠处于目标象限时间、穿越平台次数[(18.11±1.12)s,(21.83±10.26)次]高于SD+PBS组[(10.60±1.36)s,(11.50±3.94)次],差异有统计学意义( t=8.69,2.42,均 P<0.05)。SD组小鼠海马组织IGF-1蛋白表达量[(579.38±55.95)pg/mg]较CC组[(729.13±79.46)pg/mg]降低,差异有统计学意义( t=3.83, P=0.001);SD+IGF-1组小鼠海马组织IGF-1蛋白表达量[(665.50±55.21)pg/mg]高于SD+PBS组[(563.40±76.33)pg/mg],差异有统计学意义( t=2.61, P=0.017)。SD组小鼠海马组织p-GSK3β蛋白表达(1.51±0.02)较CC组(1.47±0.03)升高,p-Akt蛋白表达(0.92±0.04)较CC组(1.18±0.05)降低,差异具有统计学意义( t=3.07, t=10.85,均 P<0.05),SD组小鼠海马组织Caspase-9表达(0.65±0.03)较CC组(0.60±0.02)升高,Bcl-2表达(0.93±0.03)较CC组(1.00±0.04)降低,差异具有统计学意义( t=3.65,3.98, P<0.05);SD+IGF-1组小鼠海马组织p-GSK3β与p-Akt蛋白表达[(1.57±0.03),(1.20±0.04)]较SD+PBS组[(1.51±0.03),(0.92±0.05)]升高,差异具有统计学意义( t=3.98,11.49,均 P<0.05),SD+IGF-1组小鼠海马组织Caspase-9表达(0.60±0.03)较SD+PBS组(0.67±0.02)降低,SD+IGF-1组小鼠海马组�Objective To explore the effects of IGF-1 on cognitive function in REM sleep deprivation model mice and its possible mechanism.Methods C57BL/6J mice aged 8 weeks were randomly divided into 4 groups with 6 mice in each group.They were Normal control group(CC group),REM sleep deprivation 5d group(SD group),REM sleep deprivation 5d+Intraperitoneal injection of IGF-1 group(SD+IGF-1 group),and REM sleep deprivation 5d+Intraperitoneal injection of PBS group(SD+PBS group).The Morris water maze was used to test the cognitive function of all mice.The content of IGF-1 in mice hippocampus was detected by Elisa,and the expression level of TNF-α,IL-1βand IL-6 mRNA in mice in hippocampus was determined by RT-qPCR.Western blot was used to detect the protein expression levels of p-GSK3β,GSK3 beta,p-Akt,Akt,Bcl-2 and Caspase-9 in mice hippocampus of each group.Results The time in the target quadrant and the number of times across the platform of the SD group((11.87±1.67)s,(12.50±5.54)times,respectively)was lower than that of the CC group((19.40±1.75)s,(22.17±8.21)times,respectively),the difference was statistically significant(t=8.71,2.26,both P<0.05).The time in the target quadrant and the number of times across the platform of the SD+IGF-1 group((18.11±1.12)s,(21.83±10.26)times),which were higher than those in the SD+PBS group((10.60±1.36)s,(11.50±3.94)times).The difference was statistically significant(t=8.69,2.42,both P<0.05).The expression of IGF-1 protein in the hippocampus of SD group((579.38±55.95)pg/mg)was lower than that of CC group((729.13±79.46)pg/mg),and the difference was statistically significant(t=3.83,P<0.05).The expression of IGF1 protein in the hippocampus of SD+IGF-1 group((665.50±55.21)pg/mg)was significantly higher than that of SD+PBS group((563.40±76.33)pg/mg),the difference was statistically significant(t=2.61,P<0.05).The expression of p-GSK3 beta protein(1.51±0.02)in mice hippocampus of SD group was higher than that of CC group(1.47±0.03),and the expression of p-Akt(0.92±0.04)was lower t

关 键 词：胰岛素样生长因子1 REM睡眠剥夺 认知功能 PI3K/AKT通路 凋亡 炎性因子 小鼠 

分 类 号：R-332[医药卫生] R74