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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(n t＝8.71，2.26，均n 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(n t＝8.69，2.42，均n 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(n t＝3.83，n 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(n t＝2.61，n 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(n t＝3.07，n t＝10.85，均n 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(n t＝3.65，3.98，n 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(n t＝3.98，11.49，均n 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组小鼠海马组织Bcl-2表达(1.00±0.03)较SD＋PBS组(0.93±0.02)升高，差异具有统计学意义(n t＝5.19，3.83，均n P<0.05)。SD组小鼠海马组织TNF-α、IL-1β、IL-6 mRNA表达水平[(3.36±0.67)，(2.00±0.40)，(4.63±0.72)]较CC组升高，差异有统计学意义(n t＝8.58，6.15，12.37，均n P<0.05)；SD＋IGF-1组小鼠海马组织TNF-α、IL-1β、IL-6 mRNA表达[(1.21±0.25)，(1.08±0.33)，(0.98±0.47)]较SD＋PBS组[(3.86±0.79)，(2.11±0.30)，(4.43±0.67)]降低，均差异有统计学意义(n t＝7.81，5.76，10.39，均n P<0.05)。n 结论:小鼠REM睡眠剥夺后认知功能下降，而腹腔注射补充IGF-1后认知功能改善，这可能与IGF-1激活PI3K/Akt信号通路，降低凋亡相关信号转导和炎性因子表达有关。“,”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-1β and 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(n t=8.71, 2.26, both n 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(n t=8.69, 2.42, both n 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 (n t=3.83, n 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 (n t=2.61, n 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 than that of CC group (1.18±0.05), The difference was statistically significant (n t=3.07, n t=10.85, both n P<0.05). The expression of Caspase-9 in mice hippocampus of SD group(0.65±0.03)was higher than that of CC group (0.60±0.02). The expression of Bcl-2 in mice hippocampus of SD group (0.93±0.03) was lower than that of CC group (1.00±0.04), and the difference was statistically significant (n t=3.65, 3.98, both n P<0.05). The expression of p-Akt and p-GSK3β protein in mice hippocamps of SD+ IGF-1 group( (1.20±0.04), (1.57±0.03)) was increased compared with those of SD+ PBS group ((0.92±0.05), (1.51±0.03)), and the difference was statistically significant (n t=3.98, 11.49, both n P<0.05). The expression of Caspase-9 in mice hippocamps of SD+ IGF-1 group (0.60±0.03) was decreased compared with that of SD+ PBS group (0.67±0.02). The expression of Bcl-2 in mice hippocampus of SD+ IGF-1 group (1.00±0.03) was increased compared with SD+ PBS group (0.93±0.02), and the difference was statistically significant (n t=5.19, 3.83, both n P<0.05). The expression level of TNF-α, IL-1β, and IL-6 mRNA in mice hippocampus of SD group ((3.36±0.67), (2.00±0.40), (4.63±0.72)) were increased compared with CC group with statistically significant differences (n t=8.58, 6.15, 2.37, all n P<0.05). The expression level of TNF-α, IL-1β, and IL-6 mRNA in mice hippocampu of SD+ IGF-1 group ((1.21±0.25), (1.08±0.33), (0.98±0.47)) were lower than those of SD+ PBS group ((3.86±0.79), (2.11±0.30), (4.43±0.67)), with statistically significant differences (n t=7.81, 5.76, 10.39, all n P<0.05).n Conclusion:The cognitive function of mice decreased after REM sleep deprivation and improved after IGF-1 supplementation, which may be related to the activation of PI3K / Akt signal pathway by IGF-1, thus reducing apoptosis related signal transduction and inflammatory factor expression.