世界中医药2025，Vol.20Issue(15)：2671-2676,2685,7.DOI:10.3969/j.issn.1673-7202.2025.15.011
二仙汤治疗早发性卵巢功能不全小鼠的机制研究
Mechanism of Erxian Decoction in the Treatment of Primary Ovarian Insufficiency in Mice
摘要
Abstract
Objective:To investigate the effects of Erxian Decoction(EXD)on ovarian morphology and follicular development in mice with premature ovarian insufficiency(POI)based on the mammalian target of rapamycin(mTOR)/eukaryotic translation initi-ation factor 4E-binding protein 1(4E-BP1)signaling pathway.Methods:Forty-eight female BALB/c mice were randomly divided into a blank group(n=8)and a modeling group(n=40)according to the random sampling method.The POI model was estab-lished by intraperitoneal injection of 4-vinylcyclohexene diepoxide(VCD).After successful modeling,mice were randomly assigned to five groups:model group,positive drug group(estradiol valerate,0.3 mL/time),low-dose EXD group(4 g/kg),medium-dose EXD group(8 g/kg),and high-dose EXD group(12 g/kg),with eight mice in each group.Drugs were administered by gavage once daily for six consecutive weeks.The ovarian and uterine indices were measured.Ovarian histopathology and follicle counts were ob-served by hematoxylin-eosin(HE)staining.Serum hormone levels,including estradiol(E2),luteinizing hormone(LH),follicle-stimulating hormone(FSH),and anti-Müllerian hormone(AMH),as well as liver and kidney function indicators,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),and serum creatinine(Cr),were deter-mined using enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of Ras homolog enriched in brain(Rheb),ribosomal protein S6 kinase 1(S6K1),and 4E-BP1 in ovarian tissues were detected by quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).The protein expression of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),mTOR,and their phosphorylated forms(p-PI3K,p-AKT,p-mTOR)in ovarian tissues was analyzed by Western blot.Results:Com-pared with the blank group,the model group showed a decreased number of growing follicles,reduced ovarian and uterine indices,lower serum levels of E2 and AMH,decreased expression of p-PI3K,p-AKT,and p-mTOR proteins,and reduced mRNA levels of Rheb,S6K1,and 4E-BP1(P＜0.01),while ALT,AST,BUN,and Cr activities showed no significant changes(P＞0.05).Com-pared with the model group,the high-dose EXD group exhibited fewer atretic follicles,increased ovarian and uterine indices,elevat-ed serum E2 and AMH levels,upregulated expression of p-PI3K,p-AKT,and p-mTOR proteins,and increased mRNA expression of Rheb,S6K1,and 4E-BP1(P＜0.05),with no significant changes in ALT,AST,BUN,or Cr activities(P＞0.05).Conclusion:EXD can improve ovarian morphology and follicular development in mice with POI,and its mechanism may be related to the activa-tion of the mTOR/4E-BPl signaling pathway.关键词
早发性卵巢功能不全/二仙汤/卵巢/卵泡发育/卵巢形态/血清激素/肝肾功能/mTOR/4E-BP1信号通路Key words
Primary ovarian insufficiency/Erxian Decoction/Ovary/Follicular development/Ovarian morphology/Serum hor-mones/Liver and kidney function/mTOR/4E-BP1 signaling pathway分类
医药卫生引用本文复制引用
周绵莉,喻小兰,施后渊,刘娅,王莉,廖慧玲..二仙汤治疗早发性卵巢功能不全小鼠的机制研究[J].世界中医药,2025,20(15):2671-2676,2685,7.基金项目
国家自然科学基金项目(82205002) （82205002）
四川省自然科学基金项目(2023NSFSC0655) （2023NSFSC0655）
西南医科大学附属中医医院科研项目(2020XYLH-023) （2020XYLH-023）
