不孕合并慢性子宫内膜炎患者种植窗期子宫内膜血管生成及影响因素分析  

Analysis of endometrial angiogenesis and its influencing factors during implantation window among infertility patients with chronic endometritis

作　　者：陈聪 李玉叶 余姝毅 武娅娅 杜晨阳 曾今诚 CHEN Cong;LI Yu-ye;YU Shu-yi;WU Ya-ya;DU Chen-yang;ZENG Jin-cheng(Dongguan Key Laboratory of Medical Bioactive Molecular Developmental&Translational Research,Guangdong Provincial Key Laboratory of Medical Immunology&Molecular Diagnostics,Guangdong Medical University,Dongguan 523808;Shenzhen Key Laboratory of Periimplantation Reproductive Immunization,Guangdong Periimplantation Reproductive Immunization Engineering Technology Research Center,Shenzhen Zhongshan Obstetrics&Gynecology Hospital,Shenzhen 518043)

机构地区：[1]广东医科大学,东莞市医学活性分子开发与转化重点实验室,广东省医学免疫与分子诊断重点实验室,东莞523808 [2]深圳中山妇产医院,深圳市围着床期生殖免疫重点实验室,广东省围着床期生殖免疫工程技术研究中心,深圳518043

出　　处：《生殖医学杂志》2025年第4期505-514,共10页Journal of Reproductive Medicine

基　　金：深圳市科创委基础研究项目(JCYJ20220530172817039)。

摘　　要：目的探讨不孕合并慢性子宫内膜炎(CE)患者种植窗期子宫内膜血管生成情况及其影响因素分析。方法选择2023年3月至2024年1月于深圳中山妇产医院就诊的53例不孕患者为研究对象,取患者进入助孕周期前一周期的子宫腔内膜组织,根据检查结果是否合并CE分为CE组(n=28)和非CE组(n=25)。采用实时荧光定量PCR法(qPCR)和免疫组织化学染色法分别检测患者种植窗期子宫内膜CD34、鞘氨醇激酶-1(Sphk1)、1-磷酸鞘氨醇受体1(S1PR1)、1-磷酸鞘氨醇受体3(S1PR3)、血管内皮生长因子A(VEGFA)、血管内皮生长因子受体2(VEGFR2)、血管生成素-2(Ang-2)的mRNA和蛋白表达情况,使用HALO病理图像分析系统定量分析CD34^(+)微血管密度及Sphk1、S1PR1、S1PR3、VEGFA、VEGFR2、Ang-2阳性细胞率,比较两组间各指标差异,利用Pearson相关分析统计分析各指标阳性细胞率与微血管密度的相关关系。结果(1)CE组患者CD34 mRNA水平和微血管密度显著低于非CE组患者(P<0.05)。(2)CE组患者Sphk1、S1PR3、VEGFA和VEGFR2的mRNA水平显著低于非CE组患者(P<0.05),两组间的S1PR1和Ang-2的mRNA水平无显著性差异(P>0.05);CE组患者Sphk1、S1PR3和VEGFA的阳性细胞率显著低于非CE组(P<0.05),而两组间S1PR1、VEGFR2、Ang-2的阳性细胞率无显著性差异(P>0.05)。(3)相关性分析结果显示,Sphk1和S1PR3阳性细胞率与微血管密度呈正相关关系(分别为r=0.523,P<0.0001;r=0.455,P=0.0006),而S1PR1、VEGFA、VEGFR2、Ang-2阳性细胞率与微血管密度无显著相关关系(P>0.05)。结论CE患者种植窗期子宫内膜存在血管生成障碍或不足,与Sphk1、S1PR3、VEGFA的表达量下调有关,可能是影响子宫内膜容受性并导致不孕的因素。Objective:To investigate the endometrial angiogenesis and its influencing factors during the implantation window in infertile patients complicated with chronic endometritis(CE).Methods:A total of 53 infertile patients treated in Shenzhen Zhongshan Obstetrics&Gynecology Hospital from March 2023 to January 2024 were recruited.The endometrial tissue of the patients just before entering the assisted pregnancy cycle was collected.According to the examination results,the patients were divided into CE group(n=28)and non-CE group(n=25).The mRNA and protein expression levels of endometrium CD34,sphingosine kinase-1(Sphk1),sphingosine 1-phosphate receptor 1(S1PR1),Sphingosine 1-phosphate receptor 3(S1PR3),vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor receptor 2(VEGFR2)and angiopoietin-2(Ang-2)during implantation window were detected by real-time quantitative fluorescent PCR(qPCR)and immunohistochemical staining,respectively.The HALO pathological image analysis system was used to quantitatively analyze the CD34+microvascular density and the positive cell rates of Sphk1,S1PR1,S1PR3,VEGFA,VEGFR2 and Ang-2.The differences of indicators were compared between the two groups.And the correlation between the positive cell rate of each factor and microvascular density was statistically analyzed by Pearson’s correlation analysis.Results:The mRNA level and microvessel density of CD34 in CE group were significantly lower than those in non-CE group(P<0.05).The mRNA levels of Sphk1,S1PR3,VEGFA and VEGFR2 in CE group were significantly lower than those in non-CE group(P<0.05),but there were no significant differences in the mRNA levels of S1PR1 and Ang-2 between the two groups(P>0.05).The positive cell rates of Sphk1,S1PR3 and VEGFA in CE group were significantly lower than those in non-CE group(P<0.05),but there were no significant differences in the positive cell rates of S1PR1,VEGFR2 and Ang-2 between the two groups(P>0.05).The correlation analysis results showed that the positive cell rates of Sphk1

关 键 词：不孕症 慢性子宫内膜炎 血管生成 鞘氨醇激酶-1 1-磷酸鞘氨醇受体 血管内皮生长因子A 血管生成素-2 

分 类 号：R711.6[医药卫生—妇产科学]