微环境中肾上腺髓质素水平与多囊卵巢综合征患者卵巢功能及炎症状态相关性研究  

A study on the correlation between adrenomedullin levels in microenvironment and ovarian function and inflammatory status in patients with polycystic ovary syndrome

作　　者：严琴 石文静 陈佳瑶 王燕妮 黄霞 薛婷婷 井宣 范俊梅 许素铭 崔向荣 武学清 Yan Qin;Shi Wenjing;Chen Jiayao;Wang Yanni;Huang Xia;Xue Tingting;Jing Xuan;Fan Junmei;Xu Suming;Cui Xiangrong;Wu Xueqing(The Second Clinical College of Medicine of Shanxi Medical University,Taiyuan 030001,China;Reproductive Medicine Center of Shanxi Children's Hospital(Shanxi Maternal and Child Health Hospital),Affiliated Children's Hospital of Shanxi Medical University,Taiyuan 030013,China;Department of Clinical Laboratory,Shanxi Provincial People's Hospital(Fifth Hospital)of Shanxi Medical University,Taiyuan 030012,China)

机构地区：[1]山西医科大学第二临床医学院,太原030001 [2]山西省儿童医院(山西省妇幼保健院)生殖医学中心、山西医科大学附属儿童医院,太原030013 [3]山西省人民医院临床检验科、山西医科大学第五临床医学院,太原030012

出　　处：《中华生殖与避孕杂志》2024年第8期798-807,共10页Chinese Journal of Reproduction and Contraception

基　　金：国家自然科学基金(82000722,82000302);山西省自然科学基金(201901D211519,201901D211546);山西省生殖与遗传研究科技培育团队(2020TD19);山西省妇幼保健院医院基金会(2022041)。

摘　　要：目的探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者卵泡液肾上腺髓质素(adrenomedullin,ADM)的表达水平及其与卵巢功能和炎症的相关性。方法收集2023年3~12月于山西省儿童医院(山西省妇幼保健院)生殖医学中心接受体外受精(in vitro fertilization,IVF)/卵胞质内单精子注射(intracytoplasmic sperm injection,ICSI)拮抗剂方案来促排卵助孕的不孕夫妻的资料进行队列研究。将PCOS患者作为PCOS组(n=20),选择同期单纯因输卵管和/或男方因素行IVF/ICSI助孕的患者作为对照组(n=20)。检测并比较两组患者一般临床资料和卵泡液中ADM、白细胞介素1β(interleukin 1β,IL-1β)、IL-18、转化生长因子β(transforming growth factorβ,TGF-β)的浓度,并以卵泡液ADM浓度为主要研究指标与其他指标进行相关性及多元线性回归分析。同时比较两组患者颗粒细胞(granulosa cells,GCs)的ADM mRNA表达、细胞周期与凋亡情况。结果与对照组相比,PCOS组患者卵泡液及GCs中ADM表达明显更低(均P<0.001),而其睾酮、黄体生成素与卵泡刺激素比值、窦卵泡计数(antral follicle count,AFC)、获卵数、卵巢敏感指数以及卵泡液IL-1β、IL-18、TGF-β更高,且均与ADM浓度呈负相关(r=-0.37,P=0.019;r=-0.32,P=0.047;r=-0.50,P<0.001;r=-0.38,P=0.017;r=-0.38,P=0.016;r=-0.44,P=0.005;r=-0.37,P=0.018;r=-0.54,P<0.001)。多元线性回归分析表明,AFC、促性腺激素启动剂量、IL-1β和TGF-β是影响局部ADM水平的独立相关因素(r=-0.37,P=0.008;r=-0.27,P=0.035;r=-0.28,P=0.028;r=-0.45,P<0.001)。两组患者GCs的周期情况差异无统计学意义(P>0.05),但PCOS组GCs凋亡率(apoptosis rate,AR)高于对照组(PCOS组AR中位数=46.07%,对照组AR中位数=28.57%,n=10,P=0.036)。结论PCOS患者卵泡液中ADM表达的降低与卵巢内分泌紊乱、多个囊泡、高卵巢反应性及局部炎症状态有关。Objective:To explore the expression levels of adrenomedullin(ADM)in follicular fluid of patients with polycystic ovary syndrome(PCOS)and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study,the data on infertile couples who received an antagonistic regimen of in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital(Shanxi Maternal and Child Health Hospital)were collected.PCOS patients were selected as the PCOS group,and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group.The general clinical data of two groups of patients were analyzed,and the expression of ADM,interleukin 1β(IL-1β),IL-18,transforming growth factorβ(TGF-β)in the follicular fluid were compared between the two groups of patients.And taking the concentration of ADM in follicular fluid as the main research indicator,correlation and multiple linear regression analysis were conducted with other indicators.Simultaneously the ADM mRNA expression,cell cycle and cell apoptosis of granulosa cells were compared between the two groups.Results:This study included 20 cases in the PCOS group and 20 cases in control group.Compared with control group,the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower(both P<0.001),while its testosterone,the ratio of luteinizing hormone and follicle-stimulating hormone,antral follicle count(AFC),number of retrieved eggs,ovarian sensitivity index,as well as IL-1β,IL-18 and TGF-βin follicular fluid were higher and negatively correlated with ADM(r=-0.37,P=0.019;r=-0.32,P=0.047;r=-0.50,P<0.001;r=-0.38,P=0.017;r=-0.38,P=0.016;r=-0.44,P=0.005;r=-0.37,P=0.018;r=-0.54,P<0.001).Multiple linear regression showed that AFC,gonadotropin initiation dose,IL-1βand TGF-βwere the independent related factors that affect local ADM levels(

关 键 词：多囊卵巢综合征 肾上腺髓质素 卵泡液 卵巢功能 炎症 

分 类 号：R711.75[医药卫生—妇产科学]