基于PI3K/Akt信号通路探讨小分子肽-SMT(S)改善失眠的分子作用机制  

Molecular mechanism of action of small molecule peptide-SMT(S)for ameliorating insomnia based upon PI3K/Akt signaling pathway

作　　者：李典育 房星宇 李辉[2] 刘健 安昱 曹占鸿 白浩楠 杨擎 李娜 LI Dianyu;FANG Xingyu;LI Hui;LIU Jian;AN Yu;CAO Zhanhong;BAI Haonan;YANG Qing;LI Na(Jilin Ginseng Research Institute,Changchun University of Chinese MedicineJilin Changchun 130117,China;Department of General Surgery,Jilin Qianwei Hospital,Jilin Changchun 130012,China)

机构地区：[1]长春中医药大学吉林省人参科学研究院,吉林长春130117 [2]吉林省前卫医院普外科,吉林长春130012

出　　处：《中国医院药学杂志》2024年第17期2001-2007,共7页Chinese Journal of Hospital Pharmacy

摘　　要：目的:探讨SMT(S)改善小鼠失眠及失眠引起的继发性认知障碍、焦虑、免疫低下的作用机制。方法:应用PCPA建立失眠小鼠动物模型,通过行为学实验以及检测血清中神经递质含量,考察SMT(S)的镇静催眠作用以及改善焦虑和学习记忆能力;通过NK细胞杀伤实验和T淋巴细胞转化实验检测增强免疫功能的能力,应用Western blotting检测PI3K/Akt信号通路蛋白表达情况。结果:SMT(S)可减少失眠小鼠在旷场中央格停留时间、移动距离及平均速度,缩短在水迷宫中的上岸潜伏期及总路程;增加血清中5-HT含量以及减少DA和NE的含量;升高NK细胞杀伤率及淋巴细胞刺激指数;增加了PI3K、Akt、mTOR蛋白在失眠小鼠脑组织中的表达。结论:SMT(S)可有效预防失眠,明显改善失眠后小鼠的学习记忆能力及焦虑情况,并增强小鼠的免疫功能,其分子机制与调节PI3K/Akt信号通路相关。实验表明SMT(S)通过调节PI3K/Akt信号通路治疗失眠及失眠引起的继发性认知障碍、焦虑、免疫力低下的作用。OBJECTIVE To explore the mechanism of action of SMT(S)in ameliorating insomnia and insomnia-induced secondary cognitive impairment,anxiety and immunodeficiency in mice.METHODS Para-chlorophenylalanine(PCPA)was applied for establishing an animal model of insomniac mice.Sedative-hypnotic effect of SMT(S)as well as improvement of anxiety and capability of learning and memory were explored through behavioral experiments and detecting neurotransmitter contents in sera.Capability of enhancing immune function was detected by NK cell killing and T-lymphocyte transformation assays and Western blot was applied for detecting the protein expressions of PI3K/Akt signaling pathway.RESULTS SMT(S)reduced residence time,distance traveled and average speed of insomniac mice in central compartment of open field and shortened the latency to disembarkation and total distance traveled in water maze;boosted the serum level of 5-HT as well as lowered the levels of DA and NE;elevated the rate of NK-cell killing and index of lymphocyte stimulation;and up-regulated the expressions of PI3K,Akt and mTOR proteins in brain tissues of insomniac mice.CONCLUSION SMT(S)may effectively prevent insomnia,significantly improve learning/memory capability and anxiety and enhance immune function in insomniac mice.Its molecular mechanism is correlated with the regulation of PI3K/Akt signaling pathway.Thus SMT(S)treats insomnia and insomnia-induced secondary cognitive impairment,anxiety and immuno compromise through regulating the signaling pathway of PI3K/Akt.

关 键 词：SMT(S) 失眠 免疫 PI3K/AKT 

分 类 号：R285[医药卫生—中药学] R965[医药卫生—中医学]