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Study on the effect of Shugeng Jieyu Prescription on apoptosis of astrocytes in perimenopausal depression rats by regulating PI3K/AKT signaling pathway
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DOI   10.11656/j.issn.1672-1519.2025.10.15
Key Words   perimenopausal depression;PI3K/Akt;cell apoptosis;astrocytes
Author NameAffiliationE-mail
WANG Tian Center for Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China  
LIU Jinyu Center for Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China  
ZHANG Ziying Center for Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China  
CAO Xue Center for Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China  
JIANG Bo Center for Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China Jbhzf8224099@163.com 
Abstract
    Objective To investigate the mechanism of Shugeng Jieyu Prescription in regulating the apoptosis of astrocytes(AST) in perimenopausal depression(PMD) rats through phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway.Methods PMD model was established by bilateral ovariectomy combined with chronic unpredictable mild stress(CUMS) in rats. The successful model rats were randomly divided into model group, Shugeng Jieyu Prescription low[2.9 g/(kg·d)], medium[5.8 g/(kg·d)], high dose group[11.6 g/(kg·d)] and Xiaoyao Powder group, 10 rats in each group, and sham operation group was set as control. Stress stimulation was given for 28 consecutive days, and the rats in the treatment group were given intragastric administration. The degree of depression was evaluated by sucrose preference test, forced swimming test and novelty feeding test. The concentration of corticotropin-releasing hormone(CRH), adrenocorticotropic hormone(ACTH) and corticosterone(CORT) in hippocampus was detected by ELISA. The expression of glial fibrillary acidic protein(GFAP) protein in hippocampus was detected by immunohistochemistry. The expression of Caspase-3, B-cell lymphoma-2(Bcl-2), BCL-2-associated X protein(Bax), phosphorylated PI3K and phosphorylated Akt protein in hippocampus was detected by Western blot. The co-localization of GFAP with Bax, Bcl-2 and Caspase-3 protein was detected by immunofluorescence co-localization.Results The rats in the model group showed depression-like behavior, the concentration of CRH, ACTH and CORT in hippocampus increased, the expression of GFAP, Bcl-2, P-PI3K and P-Akt decreased, the expression of Bax and Caspase-3 increased, the number of Bax positive cells and fluorescence fusion increased, and the number of Bcl-2 positive cells and fluorescence fusion decreased. The high and middle dose groups of Shugeng Jieyu Prescription could significantly improve depression-like behavior, reduce the concentration of CRH, ACTH and CORT in hippocampus, up-regulate the expression of GFAP, Bcl-2, P-PI3K and P-Akt, down-regulate the expression of Bax and Caspase-3, reduce Bax positive cells and fluorescence fusion, and increase Bcl-2 positive cells and fluorescence fusion(P < 0.01 or P < 0.05).Conclusion Shugeng Jieyu Prescription can activate PI3K/Akt signaling pathway, inhibit the apoptosis of hippocampal AST, and treat PMD.

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