基于靶向代谢组学探究定坤丹对高龄低预后性不孕症患者卵泡液代谢微环境的调控作用OA
Investigating the Regulatory Effect of Dingkun Dan on the Metabolic Microenvironment of Follicular Fluid in Elderly Patients with Poor-Prognosis Infertility Based on Targeted Metabolomics
[目的]探讨补肾健脾中成药定坤丹对高龄低预后性不孕症患者卵泡液代谢微环境的调控作用.[方法]随机选取2024年1月至2025年1月于山东中医药大学附属医院行体外受精-胚胎移植(IVF-ET)的高龄低预后性不孕症患者30例,根据患者前期治疗药物分为定坤丹组15例和安慰剂组15例.取卵日留取的卵泡液样本5 mL,采用 UHPLC-QTRAP MS 定量代谢组学技术,以P＜0.05 为标准筛选差异代谢物,并进行多维统计分析与生物信息学分析.[结果]通过卵泡液靶向代谢组学技术共筛选出差异代谢物13种,其中上调的有6种,下调的有7种,上调的代谢物主要有L-苹果酸(L-malic acid)、5-羟基色氨酸(5-hydroxy-L-tryptophan)、2-羟基丁酸(2-hydroxybutyric acid)、α-羟基异丁酸(alpha-hydroxyisobutyric acid)、N-乙酰-L-丙氨酸(N-acetyl-L-alanine)等;下调的代谢物主要有β-丙氨酸(beta-alanine)、肌氨酸(sarcosine)、L-丙氨酸(l-alanine)、1H-吲哚-3-乙酰胺(1H-indole-3-acetamide)、吡咯-2-羧酸(pyrrole-2-carboxylic acid)、N-乙酰色氨酸(N-acetyltryptophan)等.主要归属为氨基酸类、羟基酸类、吲哚类、苯环型化合物类、吡咯类等5类.[结论]定坤丹可能通过调节卵泡液代谢微环境,增强抗氧化能力,改善卵母细胞质量,从而提高高龄低预后性不孕症患者的IVF-ET妊娠结局.
Objective To explore the regulatory effect of Dingkun Dan,a traditional Chinese medicine(TCM)formula for tonifying the kidney and invigorating the spleen,on the metabolic microenvironment of follicular fluid in elderly patients with poor-prognosis infertility.Methods Thirty elderly patients with poor-prognosis infertility undergoing in vitro fertilization-embryo transfer(IVF-ET)at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2024 to January 2025 were randomly selected.Based on the prior treatment medication,the patients were divided into a Dingkun Dan group(n=15)and a placebo group(n=15).Follicular fluid samples(5 mL)collected on the day of oocyte retrieval were analyzed using UHPLC-QTRAP MS quantitative metabolomics technology.Differential metabolites were screened based on a P-value＜0.05,followed by multivariate statistical analysis and bioinformatic analysis.Results A total of 13 differential metabolites were screened out from the follicular fluid through targeted metabolomics,among which 6 were upregulated and 7 were downregulated.The upregulated metabolites mainly included L-malic acid,5-hydroxy-L-tryptophan,2-hydroxybutyric acid,alpha-hydroxyisobutyric acid,and N-acetyl-L-alanine.The downregulated metabolites mainly included beta-alanine,sarcosine,l-alanine,1H-indole-3-acetamide,pyrrole-2-carboxylic acid,and N-acetyltryptophan.These metabolites primarily belonged to five categories:amino acids,hydroxy acids,indoles,benzene-ring compounds,and pyrroles.Conclusion Dingkun Dan may potentially improve the IVF-ET pregnancy outcomes in elderly patients with poor-prognosis infertility by regulating the metabolic microenvironment of follicular fluid,enhancing antioxidant capacity,and improving oocyte quality.
张江琳;高丹丹;孙振高
山东中医药大学第一临床医学院,山东 济南 250014山东中医药大学第一临床医学院,山东 济南 250014山东中医药大学附属医院生殖与遗传科,山东 济南 250014
医药卫生
补肾健脾定坤丹高龄低预后性不孕症体外受精-胚胎移植妊娠结局卵泡液代谢微环境靶向代谢组学
tonifying kidney and invigorating spleenDingkun Danelderlypoor-prognosis infertilityin vitro fertilization-embryo transfer(IVF-EF)pregnancy outcomefollicular fluidmetabolic microenvironmenttargeted metabolomics
《广州中医药大学学报》 2026 (4)
936-944,9
国家重点研发计划项目(编号:2022YFC3500403)国家自然科学基金项目(编号:82274572)山东省重点研发计划项目(编号:2023CXGC010505)
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