Study on mechanism of hesperidin regulating Akt/mTOR signaling pathway in hippocampus of chronic stress depression model rats
10.3969/j.issn.1000-484X.2024.12.015
- VernacularTitle: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
- Author:
Yu LEI
1
;
Wei LIU
;
Li BAO
Author Information
1. 武汉市精神卫生中心精神科,武汉 430022
- Keywords:
Hesperidin;
Chronic stress depression;
Protein kinase B;
Mammalian target of rapamycin;
Hippocampus
- From:
Chinese Journal of Immunology
2024;40(12):2548-2553
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore whether hesperidin participates in affecting the chronic stress depression model rat by regu-lating 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 hesperi-din group,low-dose hesperidin group,fluoxetine group,hesperidin+Akt inhibition group,with 12 per group.A rat model of stress-in-duced 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 ob-served by HE staining and Tunel staining;the contents of corticosterone(CORT),5-hydroxytryptamine(5-HT)and IL-6 in hippo-campus 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 num-ber 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 hesperidin group and the hesperidin+Akt inhibition group recovered slowly,the immobility time of tail suspension,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 fluoxetine group,the hesperidin high-dose group had no significant dif-ference in each index(P>0.05).Conclusion:Hesperidin regulates the Akt/mTOR pathway to activate Akt and mTOR,relieve neuro-nal apoptosis,and improve the neurological and behavioral functions of depressed rats,thereby treating chronic stress depression.