南方医科大学学报2025,Vol.45Issue(11):2340-2349,10.DOI:10.12122/j.issn.1673-4254.2025.11.06
枸杞多糖通过下调miR-23a减轻顺铂诱导的颗粒细胞损伤
Lycium barbarum polysaccharides alleviates cisplatin-induced granulosa cell injury by downregulating miR-23a
摘要
Abstract
Objective To evaluate the protective effect of Lycium barbarum polysaccharides(LBP)against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms.Methods Human granulosa-like tumor cell line(KGN)were treated with 2.5 µg/mL cisplatin for 24 h,followed by treatment with 100,500,and 1000 mg/L LBP,and the changes in cell viability,apoptosis,level of anti-Müllerian hormone(AMH),and cell ultrastructure were detected with CCK-8 assay,flow cytometry,ELISA and transmission electron microscopy.The cellular expressions of Bax,caspase-3,Bcl-2,and the PI3K/AKT pathway proteins were analyzed using Western blotting,and the expression of miR-23a was detected with RT-qPCR.KGN cell models with lentivirus-mediated miR-23a overexpression or knockdown were used to verify the therapeutic mechanism of LBP.Results Cisplatin treatment significantly inhibited cell viability,induced apoptosis,decreased AMH level,caused ultrastructural abnormalities,increased Bax and caspase-3 expression,and lowered Bcl-2 expression in KGN cells.Cisplatin also suppressed the activation of the PI3K/AKT signaling pathway and upregulated miR-23a expression in the cells.LBP intervention obviously alleviated cisplatin-induced injuries in KGN cells,and in particular,LBP treatment at the medium dose for 24 h significantly improved KGN cell viability,reduced apoptosis,enhanced their endocrine function,and ameliorated ultrastructural abnormalities.Mechanistically,medium-dose LBP obviously activated the PI3K/AKT pathway by downregulating miR-23a in cisplatin-treated cells,subsequently inhibiting Bax and caspase-3 while upregulating Bcl-2.Overexpression of miR-23a weakened while knockdown of miR-23a significantly enhanced the protective effects of LBP.Conclusion LBP alleviates cisplatin-induced apoptosis in KGN cells by inhibiting miR-23a expression and activating the PI3K/AKT pathway,suggesting a potential therapeutic strategy for ovarian function preservation.关键词
枸杞多糖/miR-23a/KGN/细胞凋亡/PI3K/AKT信号通路Key words
Lycium barbarum polysaccharides/miR-23a/KGN cells/cell apoptosis/PI3K/AKT signaling pathway引用本文复制引用
刘柳青,王坤,王雪晴,杜冰心..枸杞多糖通过下调miR-23a减轻顺铂诱导的颗粒细胞损伤[J].南方医科大学学报,2025,45(11):2340-2349,10.基金项目
新安医学教育部重点实验室开放课题(2024xayx12) (2024xayx12)
安徽中医药大学徽学研究中心开放基金科研项目(2024HXYJZX11) (2024HXYJZX11)
安徽省高等学校自然科学研究项目(2022AH050494) (2022AH050494)
安徽中医药大学第一批高层次人才支持计划(2022rcyb003) (2022rcyb003)
安徽中医药大学科研基金项目(2021zrzd13) (2021zrzd13)