高雄激素诱导小鼠颗粒细胞氧化应激与炎症的研究  

Study on hyperandrogen-induced oxidative stress and inflammation in mouse granulosa cells

作　　者：翟怡 庞艳莉 ZHAI Yi;PANG Yanli(Reproductive Medical Center,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院生殖医学中心,北京100191

出　　处：《中国生育健康杂志》2024年第2期122-128,共7页Chinese Journal of Reproductive Health

基　　金：国家自然科学基金(82022028,82171627,82288102);北京大学第三医院临床重点项目(BYSYZD2019020)。

摘　　要：目的探究高雄激素对颗粒细胞基因表达的广泛影响,为多囊卵巢综合征(PCOS)局部高雄的分子机制和干预靶点研究提供参考。方法通过获取小鼠颗粒细胞,体外添加DHEA或等量DMSO培养,通过转录组测序技术对比DHEA组和对照组基因差异表达情况,进行GO、KEGG和GSEA富集分析。结果DHEA处理组的颗粒细胞相较于对照组有355个基因显著下调,577个基因显著上调,组间差异明显。PPAR信号通路,谷胱甘肽代谢,精氨酸生物合成,单环β-内酰胺类抗生素生物合成,cAMP信号通路,mTORC1信号,未折叠蛋白响应,活性氧途径,氧化磷酸化和上皮间质转化等被显著富集。结论DHEA处理激活了小鼠颗粒细胞氧化应激和炎症相关的通路,诱导细胞凋亡,但各通路对PCOS的影响程度和机制仍需进一步实验验证。Objective To explore the extensive effects of hyperandrogen on granulosa cell gene expression,and to provide reference for the molecular mechanism and intervention targets of local hyperandrogen in polycystic ovary syndrome(PCOS).Methods Mouse granulosa cells were obtained and cultured with DHEA or equivalent amount of DMSO in vitro.Gene differential expression in DHEA group and control group were compared by transcriptome sequencing technology,and GO,KEGG and GSEA enrichment analysis was conducted.Results Compared with the control group,355 genes were significantly down-regulated and 577 genes were significantly up-regulated in the granulosa cells treated with DHEA,showing significant differences between two groups.PPAR signaling pathway,glutathione metabolism,arginine biosynthesis,monobactam biosynthesis,cAMP signaling pathway,mTORC1 signaling,unfolded protein response,reactive oxygen pathways,oxidative phosphorylation and epithelial interstitial transformation were significantly enriched.Conclusion This study suggests that DHEA treatment activated oxidative stress and inflammatory pathways in mouse granulosa cells to induce apoptosis,but the degree of influence and mechanism of each pathway on PCOS still need further experimental verification.

关 键 词：多囊卵巢综合征(PCOS) 颗粒细胞 雄激素 转录组 

分 类 号：R33[医药卫生—人体生理学]