实用临床医药杂志2025，Vol.29Issue(12)：38-43,49,7.DOI:10.7619/jcmp.20250451
氟西汀通过调节PI3K/AKT/mTOR信号通路减轻慢性不可预见的温和应激大鼠抑郁样行为
Fluoxetine alleviates depressive-like behaviors in chronic unpredictable mild stress rats by regulating PI3K/AKT/mTOR signaling pathway
摘要
Abstract
Objective To investigate the effect of fluoxetine(FLX)in allivating depressive-like behaviors in chronic unpredictable mild stress(CUMS)rats through regulation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway.Methods Twenty-four rats were randomly divided into four groups according to random number table method:Con group(healthy rats),CUMS group(CUMS-induced depressive rat model),FLX group(CUMS-induced depressive rat model intraperitoneally injected with 10 mg/kg FLX),and LY294002 group(CUMS-induced depressive rat model intraperitoneally injected with 0.002 μg/kg LY294002),with six rats in each group.The rats were exposed to a chronic unpredictable stress(CUS)environ-ment to establish depressive model.Behavioral indicators of rats in each group were observed and recorded,including sucrose preference test,immobility duration in the tail suspension test,and the immobility time in the forced swimming test.The levels of adrenocorticotropic hormone(ACTH),cortisol(CORT),interleukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)in the serum of rats in each group were detected.The content of brain-derived neurotrophic factor(BDNF)in the hippocampal tissue was detected by immunohistochemistry.The expression levels of related proteins in the PI3K/AKT/mTOR signaling pathway were detected by Western blotting.Results Compared with the Con group,the CUMS group showed a decreased sucrose preference rate,BDNF level,p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR,as well as prolonged immobility duration in the tail suspension test,prolonged immobility time in the forced swimming test,and increased levels of ACTH,CORT,IL-1β,IL-6,and TNF-α(P＜0.05).Compared with the CUMS group,the FLX group exhibited an increased sucrose preference rate,BDNF level,p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR,as well as shortened immobility duration in the tail suspension test,shortened immobility time in the forced swimming test,and decreased levels of ACTH,CORT,IL-1 β,IL-6,and TNF-α,with statistically significant differences(P＜0.05).Compared with the FLX group,the LY294002 group showed a decreased sucrose preference rate,BDNF level,p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR,as well as prolonged immobility duration in the tail suspension test,prolonged immobility time in the forced swimming test,and increased levels of ACTH,CORT,IL-1β,IL-6,and TNF-α,with statistically significant differences(P＜0.05).Conclusion FLX can regulate the secretion of ACTH,CORT,and BDNF,inhibit neuroinflammation,and improve depres-sive-like behaviors in CUMS rats,possibly by activating the PI3K/AKT/mTOR signaling pathway.关键词
氟西汀/磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路/抑郁/慢性不可预见的温和应激/悬尾实验/强迫游泳实验/促肾上腺皮质激素/脑源性神经营养因子分类
医药卫生引用本文复制引用
葛恒梅,咸振萍..氟西汀通过调节PI3K/AKT/mTOR信号通路减轻慢性不可预见的温和应激大鼠抑郁样行为[J].实用临床医药杂志,2025,29(12):38-43,49,7.基金项目
江苏省优势学科建设工程项目(YSHL2201-1050) （YSHL2201-1050）
