摘要
目的分析多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者和非PCOS患者在持久性有机污染物(persistent organic pollutants,POPs)多氯联苯(polychlorinated biphenyls,PCBs)暴露、炎症水平和氧化应激水平间的差异,并探究PCBs暴露与PCOS发生及其与炎症、代谢异常的关联。方法采用病例-对照研究选取2013年4月至2013年9月期间在北京大学第三医院妇产科生殖医学中心接受体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)的体质量正常PCOS患者(PCOS组,n=30)和非PCOS患者(对照组,n=25),收集受试者的一般资料、临床数据,测定血清中25种PCBs、炎症因子、氧化应激水平,并对污染物、炎症水平和氧化应激水平及临床指标间的相关性进行分析,对PCBs、炎症因子、氧化应激水平在PCOS发病中的作用进行分析,进一步探究睾酮在PCBs同系物总水平(SPCBs)与炎症因子白细胞介素-6(interleukin-6,IL-6)水平之间的中介效应。结果对PCBs的检测显示PCOS组中8种PCBs显著高于对照组(均P<0.05),并且PCBs水平、类二噁英类PCB同系物总和(dl-PCBs)水平显著高于对照组(P=0.037、P=0.002);PCOS组IL-6、晚期氧化蛋白产物(advanced oxidation protein products,AOPPs)、晚期糖基化终末产物(advanced glycation end products,AGEs)水平显著高于对照组(P=0.005、P=0.021、P=0.034)。研究人群中,PCBs、dl-PCBs、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、IL-6、AOPPs、AGEs都和睾酮呈显著正相关(r=0.58,P<0.001;r=0.53,P<0.001;r=0.70,P<0.001;r=0.57,P<0.001;r=0.69,P<0.001;r=0.57,P=0.003)。多因素回归模型中,PCBs(OR=1.016,95%CI=1.001~1.030,P=0.031)、TNF-α(OR=2.415,95%CI=1.058~5.510,P=0.036)、IL-6(OR=1.865,95%CI=1.126~3.089,P=0.015)、AOPP(OR=1.155,95%CI=1.002~1.332,P=0.047)均与PCOS的发生风险有关。睾酮在PCBs对IL-6的作用中有显著的中介效应(中介效应占比47.20%)。结论PCOS患者血清中PCBs水平显著升高,炎症指标和氧化应激水平也高于非PCOS患者,睾酮在PCBs对IL-6的作用中存在中介效应。
Objective To analyze the differences in exposure of persistent organic pollutants(POPs)polychlorinated biphenyls(PCBs),inflammation levels and oxidative stress levels between patients with and without polycystic ovary syndrome(PCOS),and to explore the relationship between PCBs exposure and the incidence of PCOS,and its association with inflammation and metabolic abnormalities.Methods This case-control study enrolled normal weight PCOS patients(PCOS group,n=30)and control participants without PCOS(control group,n=25)who received in vitro fertilization and embryo transfer(IVF-ET)in Reproductive Medicine Center,Department of Obstetrics and Gynecology,Peking University Third Hospital from April 2013 to September 2013,and general information and clinical data of the subjects were collected.The serum levels of 25 kinds of PCBs,inflammatory factors,and oxidative stress indicators were measured.Then we analyzed the correlation between pollutants,inflammation levels,oxidative stress and clinical indicators,and explored the effect of these indicators in the pathogenesis of PCOS.Furthermore,we explored the mediating effect of testosterone in the relationship between the sum of PCB congeners(ƩPCBs)and interleukin-6(IL-6)levels.Results We found that 8 kinds of PCBs were significantly higher in PCOS group(all P<0.05),and the levels ofƩPCBs and the sum of dioxin-like-PCBs(Ʃdl-PCBs)were significantly higher than those in control group(P=0.037,P=0.002).The inflammatory factor IL-6 was significantly higher in PCOS group than in control group(P=0.005).As for oxidative states,advanced oxidation protein products(AOPPs)and advanced glycation end products(AGEs)levels in PCOS group were significantly higher than those in the control(P=0.021,P=0.034).In studied population,ƩPCBs,Ʃdl-PCBs,tumor necrosis factor-α(TNF-α),IL-6,AOPPs and AGEs were positively correlated with testosterone(r=0.58,P<0.001;r=0.53,P<0.001;r=0.70,P<0.001;r=0.57,P<0.001;r=0.69,P<0.001;r=0.57,P=0.003).And multiple regression analysis confirmed thatƩPCBs(OR=1.016,95%CI=1.001-1.030,P=0.031),TNF-α(OR=2.415,95%CI=1.058-5.510,P=0.036),IL-6(OR=1.865,95%CI=1.126-3.089,P=0.015)and AOPPs(OR=1.155,95%CI=1.002-1.332,P=0.047)were associated with the risk of PCOS.Testosterone had a significant mediation effect in the effect ofƩPCBs on IL-6(mediation effect accounts for 47.20%).Conclusion The level of PCBs in the serum of PCOS patients is significantly increased,and the levels of inflammation and oxidative stress indicators are also higher than those of the control.Testosterone has a mediating effect in the effect of PCBs on IL-6.
作者
张玉瑢
张春梅
赵越
Zhang Yurong;Zhang Chunmei;Zhao Yue(Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China)
出处
《中华生殖与避孕杂志》
CAS
CSCD
北大核心
2022年第11期1167-1175,共9页
Chinese Journal of Reproduction and Contraception
基金
国家重点研发计划课题(2021YFC2700402)
中国医学科学院医学与健康科技创新工程项目资助(2019-I2M-5-001)。
关键词
多囊卵巢综合征
持久性有机污染物
多氯联苯
炎症
氧化应激
Polycystic ovary syndrome
Persistent organic pollutants
Polychlorinated biphenyls
Inflammation
Oxidative stress
