大黄酚脂质体改善异氟烷致小鼠记忆功能减退的作用及对PI3K/Akt信号通路的影响  

Effect of Chrysophanol Liposomes on Memory Impairment Induced by Isoflurane in Mice and Influence on PI3K/Akt Signaling Pathway

作　　者：贺信[1] 李玉清[1] 童学飞[1] 王媛媛[1] He Xin;Li Yuqing;Tong Xuefei;Wang Yuanyuan(Department of Pharmacy,Shiyan Traditional Chinese Medicine Hospital,HubeiShiyan 442000,China)

机构地区：[1]十堰市中医医院药剂科,湖北十堰442000

出　　处：《中国药师》2019年第5期823-827,共5页China Pharmacist

摘　　要：目的:探讨大黄酚脂质体改善异氟烷致小鼠记忆功能减退的作用及对PI3K/Akt信号通路的影响。方法:昆明种小鼠80只随机分为4组:正常对照组(连续7 d腹腔注射生理盐水后吸氧2 h)、大黄酚脂质体组(连续7 d腹腔注射大黄酚脂质体10 mg·kg^(-1)后吸1. 5%异氟烷2 h)、模型组(连续7 d腹腔注射生理盐水后吸1. 5%异氟烷2 h)、大黄酚脂质体+PI3K抑制剂组(连续7 d腹腔注射大黄酚脂质体10 mg·kg^(-1)+LY294002 5 mg·kg^(-1)后吸1. 5%异氟烷2 h),麻醉结束进行Morris水迷宫试验、旷场实验和条件恐惧性实验,测定小鼠海马组织中PI3K、Akt mRNA及蛋白水平。结果:与正常对照组比较,模型组逃避潜伏期显著增加,经过原平台位置的次数、原平台象限停留的时间、运动总距离、中心区域活动时间、环境诱发僵直时间、声音诱发僵直时间、PI3K和Akt mRNA水平及蛋白水平显著降低(P <0. 05)。与模型组比较,大黄酚脂质体组和大黄酚脂质体+PI3K抑制剂组的各项指标差异均有统计学意义(P <0. 05)。大黄酚脂质体组与大黄酚脂质体+PI3K抑制剂组的各项指标差异也有统计学意义(P <0. 05)。结论:大黄酚脂质体改善异氟烷致小鼠记忆功、认知功能能减退,其机制与大黄酚脂质体活化PI3K/Akt信号通路,导致海马组织内PI3K、Akt mRNA蛋白水平升高有关。Objective:To investigate the effect of chrysophanol liposomes on memory impairment induced by isoflurane in mice and their influence on PI3 K/Akt signaling pathway.Methods:Totally 80 Kunming mice were divided into 4 groups:the normal control group(oxygen inhalation 2 h after intraperitoneal injection of normal saline),chrysophanol liposomes group(peripheral injection of 10 mg·kg^-1 chrysophanol liposomes for 7 d and inhalation of 1.5%isoflurane for 2 h),the model group(peripheral injection of normal saline for 7 d and inhalation of 1.5%isoflurane for 2 h),and chrysophanol liposomes plus PI3 K inhibitor group(peripheral injection of 10 mg·kg^-1 chrysophanol liposome plus 5 mg·kg^-1 LY294002 for 7 d and inhalation of 1.5%isoflurane for 2 h).After the anesthesia,Morris water maze test,open-field experiment and conditional fear experiment were carried out.The levels of PI3 K,Akt mRNA and protein in hippocampus of mice were also determined.Results:Compared with the normal control group,in the model group,the escape latency increased significantly,and the number of times passing through the original platform,the duration of the original platform quadrant,the total distance of movement,the activity time of the central region,the time of environment-induced stiffness,the time of sound-induced stiffness,and the levels of PI3 K,Akt mRNA and protein all decreased significantly(P<0.05).Compared with the model group,there were significant differences in the indices of chrysophanol liposomes group and chrysophanol liposomes plus PI3 K inhibitor group(P<0.05).There were also significant differences in the indices between chrysophanol liposomes group and chrysophanol liposome plus PI3 K inhibitor group(P<0.05).Conclusion:Chrysophanol liposomes improve the memory function and cognitive function in isoflurane induced mice.The mechanism is related to the activation of PI3 K/Akt signaling pathway by chrysophanol liposomes,which leads to the increase of PI3 K and Akt mRNA levels in hippocampus.

关 键 词：大黄酚脂质体 异氟烷 记忆功能减退 PI3K/AKT 

分 类 号：R965.1[医药卫生—药理学]