广东医学2025，Vol.46Issue(9)：1309-1315,7.DOI:10.13820/j.cnki.gdyx.20251924
高雄激素介导PCOS小鼠卵巢免疫微环境紊乱驱动颗粒细胞凋亡及小檗碱的保护作用
Hyperandrogenism-mediated ovarian immune microenvironment dysregulation drives granulosa cell apoptosis in PCOS mice and the protective effect of Berberine
摘要
Abstract
Objective To investigate the role of hyperandrogenism-mediated inflammatory responses in ovarian dysfunction in polycystic ovary syndrome(PCOS),and to explore the protective effects of Berberine(BBR)on ovarian immune microenvironment and reproductive function in PCOS mice,providing experimental evidence for clinical prevention and treatment.Methods A PCOS mouse model was established by subcutaneous injection of dehydroepiandrosterone[DHEA,6 mg/(100 g·d)]for 21 consecutive days.Body weight and estrous cycles were measured.Ovarian morpholo-gy was examined by H&E staining.Serum testosterone,anti-Müllerian hormone(AMH),and tumor necrosis factor-α(TNF-α)levels were detected using ELISA.In vitro,THP-1 cells were treated with 0,10,50,100 μmol/L testoster-one to induce M1 polarization;TNF-α expression was assessed by RT-qPCR and ELISA.KGN cells were treated with 10 μmol/L testosterone combined with varying concentrations of TNF-α;cell viability was measured by CCK-8 assay,and PI3K phosphorylation was analyzed by Western blot.In vivo,BBR[150 mg/(kg·d),oral]was administered for 14 days,and its effects on ovarian histology,estrous cycles,and serum markers were evaluated.Results Compared with controls,PCOS mice showed significant weight gain(P＜0.05),disrupted estrous cycles,cystic ovarian enlargement,and thinning of granulosa cell layers.Serum testosterone[(3.57±1.27)ng/mL vs.(1.31±0.23)ng/mL],AMH[(1 116.27±109.85)pg/mLrs.(770.54±111.27)pg/mL],and TNF-α[(35.18±6.75)pg/mL vs.(12.37±1.38)pg/mL]levels were significantly elevated(P＜0.05).In vitro,testosterone treatment significantly increased TNF-α mRNA(1.01±0.15 vs.1.24±0.2 vs.5.31±0.21 vs.6.18±0.5)and protein expression(1±0 vs.0.96±0.07 vs.1.21±0.12 vs.1.31±0.08)in M1 macrophages(P＜0.05).Combined testosterone and high TNF-α treatment markedly reduced KGN cell viability(P＜0.05)and inhibited PI3K phosphorylation(1±0 vs.0.54±0.12 vs.0.27±0.08,P＜0.05).BBR intervention improved ovarian histopathology,restored regular estrous cycles,and significantly re-duced serum testosterone[(12.26±1.29)ng/mL vs.(32.1±5.71)ng/mL vs.(17.07±1.47)ng/mL]and TNF-αlevels[(13.08±0.79)pg/mL vs.(28.51±6.3)pg/mL vs.(16.91±0.99)pg/mL](P＜0.05).Conclusion Hy-perandrogenism promotes M1 macrophage polarization and TNF-α release,exacerbating local ovarian inflammation,im-pairing granulosa cell function,and causing ovulatory dysfunction.BBR exhibits dual effects by suppressing inflammation and lowering androgen levels,suggesting its potential as an effective adjunct therapy for PCOS.关键词
多囊卵巢综合征/免疫微环境/小檗碱/高雄激素Key words
polycystic ovary syndrome/immune microenvironment/Berberine/hyperandrogenism分类
医药卫生引用本文复制引用
王友烽,莫蕙,李荔..高雄激素介导PCOS小鼠卵巢免疫微环境紊乱驱动颗粒细胞凋亡及小檗碱的保护作用[J].广东医学,2025,46(9):1309-1315,7.基金项目
广东省自然科学基金项目(2024A1515013145) （2024A1515013145）
粤港澳大湾区国际科技创新中心建设项目(粤港澳联合创新领域)(2024A0505090001) （粤港澳联合创新领域）
中国医药卫生事业发展基金项目(BJ2023YCPYJH003) （BJ2023YCPYJH003）
