子宫内膜细胞标志物与子宫内膜异位症相关性分析

Analysis of the correlation between endometrial cell markers and endometriosis

目的 研究子宫内膜细胞标志物与子宫内膜异位症(EMT)的相关性。方法 回顾性选取2019年3月至2022年3月于海南医学院第二附属医院住院治疗的42例拟行宫腹腔镜联合手术的卵巢EMT患者作为研究组,收集异位囊肿囊壁的异位内膜组织作为EMT异位内膜组,同时宫腔镜下取研究组患者的宫底部在位内膜组织作为EMT在位内膜组,选择50例输卵管因素导致不孕的拟行宫腹腔镜联合手术的患者作为对照组,宫腔镜下取对照组患者的宫底部在位内膜作为正常在位内膜组。对所有组织切片的阳性结果采用半定量式免疫组织化学结果判定,对所有组织进行蛋白质印迹法分析,测定EMT异位内膜、EMT在位内膜、正常在位内膜的ERα、ERβ、AP-1和血管内皮生长因子(VEGF)的积分光密度(IOD)值,并分析ERα、ERβ、AP-1、VEGF之间的相关性。结果 ERα、ERβ、AP-1和VEGF等细胞标志物在EMT在位内膜组、EMT异位内膜组和正常在位内膜组组织标本中均有表达,且定位于组织标本的间质细胞和腺上皮细胞。EMT在位内膜组中ERα表达明显高于EMT异位内膜组,EMT异位内膜组和EMT在位内膜组中ERα、ERβ、AP-1和VEGF的表达均明显高于正常在位内膜组,差异均有统计学意义(P<0.05)。EMT在位内膜组中ERα、VEGF表达水平均明显高于EMT异位内膜组,EMT在位内膜组中ERβ/ERα明显低于EMT异位内膜组,差异均有统计学意义(P<0.05)。EMT在位内膜组和EMT异位内膜组中ERα、ERβ、ERβ/ERα、AP-1和VEGF表达水平均明显高于正常在位内膜组,差异均有统计学意义(P<0.05)。正常在位内膜组的增生期ERαI、ERβ、AP-1和VEGF表达水平均明显高于分泌期,差异均有统计学意义(P<0.05),呈周期性变化,而EMT在位内膜组和EMT异位内膜组的ERα、ERβ、AP-1和VEGF无周期性变化。EMT异位内膜组ERβ/ERα与AP-1呈负相关(r=-0.753,P<0.05)。结论 EMT在位内膜组织中,ERα呈高表达状态,EMT在位内膜组织和异位内膜组织中,AP-1和VEGF均呈高表达状态,与EMT的发生、发展密切相关。ERα、ERβ、AP-1和VEGF在EMT在位内膜和异位内膜中均失去了在正常在位内膜的月经周期性变化,可能与EMT内膜细胞的生物学行为发生改变有关。

Objective To study the correlation between endometrial cell markers and endometriosis(EMT).Methods A total of 42 patients with ovarian EMT who were planned to undergo hysteroscopy combined with laparoscopic surgery,hospitalized in the Second Affiliated Hospital of Hainan Medical College from March 2019 to March 2022 were restrospectively analyzed as the research group.The ectopic endometrial tissue of the cyst wall of the ectopic cyst was collected as the EMT ectopic endometrium group.At the same time,the ectopic endometrial tissue of the bottom of the uterus of the study group was taken under hysteroscope as the EMT endometrial group.Fifty cases of infertility due to fallopian tube factors who are planned to undergo combined hysteroscopy and laparoscopy were seleted as the control group.Under hysteoscopy,the uterine endometrium of the control group was taken as the control ectopic endometrium group.Positive results of all tissue sections were determined by semi-quantitative immunohistochemical results.The integrated optical density(IOD)values of ERα,ERβ,AP-1,and vascular endothelial growth factor(VEGF)in EMT ectopic endometrium,EMT eutopic endometrium,and normal eutopic endometrium were measured by Western blotting,and the correlation between ERα,ERβ,AP-1,VEGF was analyzed.Results Cell markers such as ERα,ERβ,AP-1,and VEGF were expressed in tissue samples of the EMT eutopic endometrium group,EMT ectopic endometrium group,and normal eutopic endometrium group,and were localized in interstitial cells and glandular epithelial cells of the tissue samples.The expression of ERαin the EMT ectopic endometrium group was significantly higher than that in the EMT ectopic endometrium group,and the expressions of ERα,ERβ,AP-1 and VEGF in the EMT ectopic endometrium group and the ectopic endometrium group were significantly higher than those in the normal uterine endometrium group,the differences were statistically significant(P<0.05).The ERαand VEGF in the EMT ectopic endometrium group were significantly higher than those in the EMT ectopic endometrium group,and the ERβ/ERαin the EMT ectopic endometrium group were significantly lower than those in the EMT ectopic endometrium group,the differences were statistically significant(P<0.05).The IOD values of ERα,ERβ,ERβ/ERα,AP-1 and VEGF in the EMT eutopic endometrium group and the EMT eutopic endometrium group were significantly higher than those of the normal eutopic endometrium group,the differences were statistically significant(P<0.05).The ERα,ERβ,AP-1 and VEGF of the normal eutopic endometrium group were significantly higher than those in the secretory phase,the differences were statistically significant(P<0.05),showing periodic changes.However,the ERα,ERβ,AP-1 and VEGF values of the EMT eutopic and ectopic endometrium groups did not change periodically.The ERβ/ERαof the EMT ectopic endometrium group was negatively correlated with the AP-1(r=-0.753,P<0.05).Conclusion In EMT eutopic endometrium tissues,ERαis highly expressed.In EMT eutopic endometrium tissues and ectopic endometrium tissues,AP-1 and VEGF are both highly expressed,which are closely related to the occurrence and development of EMT.ERα,ERβ,AP-1 and VEGF have lost the menstrual cycle changes in the normal eutopic endometrium in both the EMT eutopic endometrium and the ectopic endometrium.This may be due to changes in the biological behavior of EMT endometrium cells.