摘要
目的研究低氧诱导因子-1α(HIF-1α)在子宫内膜异位症(EM_(S))患者血清中的表达水平及诊断价值,探讨HIF-1α对EM_(S)在位子宫内膜间质细胞上皮-间质转化(EMT)的影响。方法采用ELISA法对EM_(S)(36例,EM_(S)组)和子宫肌瘤(43例,对照组)患者血清的HIF-1α水平进行测量分析,其中EM_(S)组患者临床分期I期、Ⅱ期为EM_(S)轻度组,Ⅲ期、Ⅳ期为EM_(S)重度组。采用受试者工作特征(ROC)曲线以及曲线下面积(AUC)反应HIF-1α的诊断水平。取EM_(S)在位子宫内膜分离培养提取原代间质细胞,干扰HIF-1α表达的慢病毒和空白病毒分别转染该细胞,得到sh-HIF-1α和sh-NC两组细胞,采用Western blotting法测量EMT相关分子(N-Cadherin、vimentin、Slug)的表达;Transwell法对比两组细胞的迁移、侵袭能力;流式细胞术检测两组细胞的凋亡率。结果EM_(S)组与对照组比较,其血清HIF-1α表达水平明显增高(P<0.001);其ROC曲线及AUC结果显示HIF-1α对EM_(S)具有一定的诊断效力,子宫内膜增生期与分泌期所对应的血清HIF-1α表达差异无统计学意义(P=0.593),EM_(S)重度组患者血清HIF-1α含量显著高于EM_(S)轻度组(P<0.001)。sh-HIF-1α组细胞的N-Cadherin(P=0.013)、vimentin(P=0.045)、Slug(P=0.038)表达均降低,细胞迁移、侵袭力减弱(P均<0.001),凋亡率升高(P=0.013)。结论HIF-1α在EM_(S)患者血清中表达水平明显升高,可作为一项潜在的临床诊断指标;HIF-1α可能通过调控EMT过程影响EM_(S)的发生发展。
Objective To explore the expression level and diagnostic value of hypoxia-inducible factor-1α(HIF-1α)in the serum of patients with endometriosis(EM_(S)),and to investigate the effect of HIF-1αon epithelial mesenchymal transition(EMT)of eutopic endometrial stromal cells in EM_(S).Methods The serum HIF-1αlevels in 36 EM_(S) cases(EM_(S) group)and 43 uterine leiomyoma cases(control group)were determined with ELISA.In the EM_(S) group,patients with clinical stages I and II were classified as mild cases and those with stagesⅢandⅣwere classified as severe cases.The diagnostic value of HIF-1αwas calculated with the receiver operating characteristic(ROC)curve and the area under the curve(AUC).Primary endometrial stromal cells were isolated and cultured from eutopic endometrium with EM_(S).Sh-HIF-1αand sh-NC cells were transfected with lentivirus and blank virus respectively.The expressions of N-cadherin,vimentin and Slug were detected with Western blotting.The migration and invasion were detected with Transwell assay,and the apoptosis was determined with Flow cytometry.Results The EM_(S) group had elevated serum HIF-1α(P<0.001).The ROC curve and AUC suggested that HIF-1αhad certain diagnostic efficacy on EM_(S).There was no significant difference in the expression of HIF-1αbetween endometrial proliferative phase and secretory phase(P=0.593).The serum HIF-1αlevel in severe EM_(S) cases was significantly higher than that in mild EM_(S) cases(P<0.001).In sh-HIF-1αgroup,the expressions of N-cadherin(P=0.013),vimentin(P=0.045)and Slug(P=0.038)decreased,cell migration and invasion reduced(P<0.001),while the apoptosis rate increased(P=0.013).Conclusion HIF-1αis highly expressed in EM_(S) patients,which can be used as a potential clinical diagnostic index.HIF-1αmay affect the development of endometriosis by regulating EMT.
作者
薛源
林雪艳
徐歌
田永杰
XUE Yuan;LIN Xueyan;XU Ge;TIAN Yongjie(Department of Obstetrics and Gynecology,Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250021,Shandong,China;Department of Obstetrics and Gynecology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,Shandong,China)
出处
《山东大学学报（医学版）》
CAS
北大核心
2021年第2期41-47,共7页
Journal of Shandong University:Health Sciences
基金
山东省自然科学基金(ZR2019MH129)。
