瑞香素对抑郁症大鼠PTEN/AKT/mTOR通路及认知功能的影响  

Effects of Daphnetin on the PTEN/AKT/mTOR Pathway and Cognitive Function in Rats with Depression

作　　者：綦航 张晋兰 李秀梅 雷津平 马英英 Qi Hang;Zhang Jinlan;Li Xiumei(Department of Psychiatry 6 Ward,Shijiazhuang Eighth Hospital,Shijiazhuang,Hebei 050000;Department of Mental Rehabilitation,Cangzhou People's Hospital,Cangzhou,Hebei 061000,China)

机构地区：[1]石家庄市第八医院精神六科,河北石家庄050000 [2]沧州市人民医院精神康复科,河北沧州061000

出　　处：《四川医学》2025年第4期385-390,共6页Sichuan Medical Journal

基　　金：河北省卫生健康委会资助项目(编号:20210467)。

摘　　要：目的探讨瑞香素对抑郁症大鼠磷酸酯酶与张力蛋白同源物/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PTEN/AKT/mTOR)通路及认知功能的影响。方法通过慢性不可预测的轻度应激建立抑郁大鼠模型;将造模后的大鼠分为抑郁组、瑞香素低剂量(瑞香素-L,30 mg/kg瑞香素)组、瑞香素高剂量(瑞香素-H,90 mg/kg瑞香素)组、瑞香素-H+pcDNA3.1(空载体)组、瑞香素-H+pcDNA3.1 PTEN(PTEN过表达载体)组,并以正常大鼠为对照组,每组10只。干预结束后,水迷宫实验检测大鼠认知功能;蔗糖偏好实验、强迫游泳时间检测大鼠抑郁行为;ELISA检测血清中白细胞介素-1β(IL-1β)、IL-6以及丙二醛(MDA)、还原型谷胱甘肽(GSH)水平;尼氏染色检测海马组织形态学变化;Western Blot检测PTEN/AKT/mTOR通路相关蛋白表达。结果与对照组相比,抑郁组神经元结构紊乱,排列稀疏,大鼠穿越平台次数、蔗糖偏爱度、GSH水平、p-AKT/AKT、p-mTOR/mTOR表达显著降低,但逃避潜伏期、强迫游泳时间、IL-1β、IL-6、MDA水平、PTEN表达显著增加(P<0.05);与抑郁组相比,瑞香素-L组、瑞香素-H组大鼠神经元形态学得到改善,穿越平台次数、蔗糖偏爱度、GSH水平、p-AKT/AKT、p-mTOR/mTOR表达显著增加,但逃避潜伏期、强迫游泳时间、IL-1β、IL-6、MDA水平、PTEN表达显著降低,组间差异有统计学意义(P<0.05);与瑞香素-H+pcDNA3.1组相比,瑞香素-H+pcDNA3.1 PTEN组大鼠穿越平台次数、蔗糖偏爱度、GSH水平、p-AKT/AKT、p-mTOR/mTOR表达显著降低,但逃避潜伏期、强迫游泳时间、IL-1β、IL-6、MDA水平、PTEN表达显著增加(P<0.05)。结论瑞香素可改善抑郁症大鼠情绪与认知功能,可能与抑制PTEN表达,上调AKT/mTOR表达有关。Objective To investigate effects of Daphnetin on the phosphatase and tensin homolog deleted on chromosome ten/protein kinase B/mammalian target of rapamycin(PTEN/AKT/mTOR)pathway and cognitive function in rats with depression.Methods A depression rat model was established through chronic unpredictable mild stress.After modeling,rats were grouped into a depression group,a low dose(Daphnetin L,30 mg/kg Daphnetin)group,a high dose(Daphnetin H,90 mg/kg Daphnetin)group,a Daphnetin-H+pcDNA3.1(empty body)group,and a Daphnetin-H+pcDNA3.1 PTEN(PTEN overexpression vector)group,with normal rats as the control group,10 rats in each group.After the intervention,the water maze experiment was applied to detect the cognitive function of rats,sucrose preference experiments and forced swimming time were applied to detect depressive behavior in rats.ELISA was applied to detect interleukin-1β(IL-1β),IL-6,malondialdehyde(MDA),and reduced glutathione(GSH)in serum.Nissl staining was applied to detect morphological changes in hippocampal tissue.Western Blot was applied to detect the expression of PTEN/AKT/mTOR pathway related proteins.Results Compared with control group,neuron structure in the depression group was disordered and sparsely arranged,the number of times of crossing the platform,sucrose preference,GSH level,p-AKT/AKT,and p-mTOR/mTOR expression were obviously reduced,however,the escape latency,forced swimming time,IL-1β,IL-6,MDA,and PTEN expression were greatly increased(P<0.05).Compared with depression group,the morphology of neurons in the Daphnetin-L and Daphnetin-H groups improved,the number of times of crossing the platform,sucrose preference,GSH,p-AKT/AKT,and p-mTOR/mTOR expression were greatly increased,however,the escape latency,forced swimming time,IL-1β,IL-6,MDA,and PTEN expression were obviously reduced,with differences between groups(P<0.05).Compared with Daphnetin H+pcDNA3.1 group,the number of times of crossing the platform,sucrose preference,GSH,p-AKT/AKT,and p-mTOR/mTOR expression in the Daphnetin-H+pcDNA3

关 键 词：瑞香素 抑郁症 认知功能 PTEN/AKT/mTOR通路 大鼠 

分 类 号：R-332[医药卫生]