目的 应用蛋白组学技术探究卵巢储备功能减退(decrease ovarian reserve,DOR)和卵巢早衰(premature ovarian failure,POF)及正常对照组之间的蛋白质差异,并对差异蛋白质进行分析进一步阐明卵巢储备功能下降和卵巢早衰发生的可能机制.方法 一次性腹腔注射环磷酰胺60 mg/kg联合白消安6 mg/kg制备DOR模型小鼠,一次性腹腔注射环磷酰胺120 mg/kg联合白消安12 mg/kg制备POF模型小鼠,药物注射后连续观察小鼠动情周期,以动情周期紊乱判定造模是否成功.成功后筛选差异蛋白,运用生物信息学方法将所鉴定的差异蛋白进行功能注释及富集分析,分析其可能机制.结果 筛选出DOR中差异倍数在1.2倍以上的差异蛋白有148个,POF中有149个;富集结果显示,DOR组的差异表达蛋白主要参与了维生素B6代谢、磷酸吡哆醛合成、氧化应激等生物学过程,并在维生素B6代谢、α-亚麻酸代谢、PPAR信号等通路富集;POF组的差异表达蛋白主要参与了脂质代谢、炎症反应等生物过程,并在鞘糖脂生物合成、花生四烯酸代谢、核糖体等通路富集.结论 DOR和POF的发病机制较复杂,都参与氧化应激、炎症反应等生物学过程;α-亚麻酸信号通路可能是参与DOR发生的一条重要通路,HIST1H1C、CA3、FABP4可能是其发生的重要靶点;花生四烯酸代谢信号通路可能是POF发生的一条重要通路,HIST1H1C、D2HGDH、CYP4F3可能是其发生的重要靶点.
Objective To explore the protein differences between decreased ovarian reserve(DOR),premature ovarian failure(POF),and the normal control group using proteomic technology;and Additionally,to analyze the differ-ential proteins to further elucidate the possible mechanisms of ovarian reserve decline and premature ovarian failure.Methods DOR model mice were prepared by a single intraperitoneal injection of 60 mg/kg cyclophosphamide combined with 6 mg/kg busulfan,while POF model mice were prepared by a single intraperitoneal injection of 120 mg/kg cyclophos-phamide combined with 12 mg/kg busulfan.The mice's estrous cycles were continuously observed after drug administra-tion to determine the success of the modeling.After successful modeling,differential proteins were screened,and bioinfor-matics methods were used for functional annotation and enrichment analysis of the identified differential proteins to analyze their possible mechanisms.Results A total of 148 differential proteins with fold changes of more than 1.2 were screened in the DOR group,and 149 differential proteins were identified in the POF group.Enrichment analysis showed that the differentially expressed proteins in the DOR group were mainly involved in biological processes such as vitamin B6 metabo-lism,pyridoxal phosphate synthesis,and oxidative stress,and they were enriched in pathways such as vitamin B6 metabo-lism,α-linolenic acid metabolism,and PPAR signaling.On the other hand,the differentially expressed proteins in the POF group were mainly involved in biological processes such as lipid metabolism and inflammatory response,and they were enriched in pathways such as glycosphingolipid biosynthesis,arachidonic acid metabolism,and ribosome.Conclu-sion The pathogenesis of DOR and POF is complex,involving processes like oxidative stress and inflammatory response.The α-linolenic acid signaling pathway may be an important pathway involved in the occurrence of DOR,and HIST1H1C,CA3,and FABP4 may be important targets for its occurrence.The arachidonic acid metabolism signaling pathway may be an important pathway involved in the occurrence of POF,and HIST1H1C,D2HGDH,and CYP4F3 may be important targets for its occurrence.