橙皮苷对慢性应激抑郁模型大鼠海马组织Akt/mTOR信号通路调节机制的研究  

Study on mechanism of hesperidin regulating Akt/mTOR signaling pathway in hippocampus of chronic stress depression model rats

作　　者：雷雨[1] 刘伟[1] 包黎[1] LEI Yu;LIU Wei;BAO Li(Department of Psychiatry,Wuhan Mental Health Center,Wuhan 430022,China)

机构地区：[1]武汉市精神卫生中心精神科,武汉430022

出　　处：《中国免疫学杂志》2024年第12期2548-2553,共6页Chinese Journal of Immunology

基　　金：湖北省卫生健康委员会项目(WJ2019M016)。

摘　　要：目的:通过构建慢性应激抑郁模型大鼠模型,探究橙皮苷是否通过调控蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR),参与影响慢性应激抑郁模型大鼠病情。方法:将72只大鼠随机分为6组:健康组、慢性应激抑郁组、橙皮苷高剂量组、橙皮苷低剂量组、氟西汀组、橙皮苷^(+)Akt抑制组,每组12只。构建慢性应激抑郁模型大鼠模型,糖水偏好实验、强迫游泳实验、旷场实验观察各组大鼠行为学情况;HE染色、Tunel染色观察各组大鼠海马组织病理学变化及细胞凋亡情况;检测各组大鼠海马组织皮质酮(CORT)、5-羟色胺(5-HT)、IL-6含量;Western blot检测海马组织Akt、mTOR、p-Akt、p-mTOR表达水平。结果:健康组大鼠海马组织完整;与健康组相比,慢性应激抑郁组大鼠海马组织损伤明显,强迫游泳不动时间、凋亡指数、CORT、IL-6含量显著升高,糖水偏好度、跨格次数、站立次数、存活神经元数、5-HT含量、p-Akt/Akt、p-mTOR/mTOR显著降低(P<0.05);与慢性应激抑郁组相比,氟西汀组、橙皮苷高剂量组、橙皮苷低剂量组大鼠海马组织逐渐恢复,强迫游泳不动时间、凋亡指数、CORT、IL-6含量显著降低,糖水偏好度、跨格次数、站立次数、存活神经元数、5-HT含量、p-Akt/Akt、p-mTOR/mTOR显著升高(P<0.05);与橙皮苷高剂量组相比,橙皮苷低剂量组、橙皮苷^(+)Akt抑制组大鼠海马组织恢复缓慢,强迫游泳不动时间、凋亡指数、CORT、IL-6含量显著升高,糖水偏好度、跨格次数、站立次数、存活神经元数、5-HT含量、p-Akt/Akt、p-mTOR/mTOR显著降低(P<0.05);橙皮苷高剂量组与氟西汀组相比,各项指标差异无统计学意义(P>0.05)。结论:橙皮苷通过调控Akt/mTOR通路,激活Akt、mTOR,缓解神经细胞凋亡,改善抑郁大鼠的神经功能和行为学功能,从而治疗慢性应激抑郁。Objective:To explore whether hesperidin participates in affecting the chronic stress depression model rat by regulating protein kinase B(Akt)and mammalian target of rapamycin(mTOR)by constructing a chronic stress depression rat model.Methods:Seventy-two rats were randomly divided into 6 groups:healthy group,chronic stress depression group,high-dose hesperidin group,low-dose hesperidin group,fluoxetine group,hesperidin^(+)Akt inhibition group,with 12 per group.A rat model of stress-induced depression was constructed,and the behaviors of the rats in each group were observed by sugar water preference test,forced swimming test,and open field test;the histopathological changes and cell apoptosis in the hippocampus of rats in each group were observed by HE staining and Tunel staining;the contents of corticosterone(CORT),5-hydroxytryptamine(5-HT)and IL-6 in hippocampus of rats in each group were detected;the expression levels of Akt,mTOR,p-Akt and p-mTOR in hippocampus were measured by Western blot.Results:The hippocampus of rats in the healthy group was intact;compared with the healthy group,the hippocampal tissue of the chronic stress-depression group was obviously damaged,the immobility time of forced swimming,the apoptosis index,CORT and IL-6 contents were obviously increased,the sugar preference,the number of crossings,the number of standing,the number of surviving neurons,the 5-HT content,p-Akt/Akt,and p-mTOR/mTOR were obviously decreased(P<0.05);compared with the chronic stress depression group,the hippocampus tissue of the rats in the fluoxetine group,the high-dose hesperidin group,and the low-dose hesperidin group gradually recovered,the immobility time of forced swimming,the apoptosis index,CORT and IL-6 contents were obviously decreased,the sugar preference,the number of crossings,the number of standing,the number of surviving neurons,the 5-HT content,p-Akt/Akt,and p-mTOR/mTOR were obviously increased(P<0.05);compared with the high-dose hesperidin group,the hippocampal tissue of the rats in the low-dose hespe

关 键 词：橙皮苷 慢性应激抑郁 蛋白激酶B 哺乳动物雷帕霉素靶蛋白 海马组织 

分 类 号：R285.5[医药卫生—中药学]