低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响

doi:10.6040/j.issn.1671-7554.0.2020.1628

摘要/Abstract

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。

关键词: 子宫内膜异位症, 低氧诱导因子-1α, 上皮-间质转化, 迁移、侵袭, 细胞凋亡

Abstract: 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-1α on epithelial mesenchymal transition(EMT)of eutopic endometrial stromal cells in EM_S. Methods The serum HIF-1α levels 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 stages Ⅲ and Ⅳ were classified as severe cases. The diagnostic value of HIF-1α was 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-1α and 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-1α had certain diagnostic efficacy on EM_S. There was no significant difference in the expression of HIF-1α between endometrial proliferative phase and secretory phase(P=0.593). The serum HIF-1α level in severe EM_S cases was significantly higher than that in mild EM_S cases(P<0.001). In sh-HIF-1α group, 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-1α is highly expressed in EM_S patients, which can be used as a potential clinical diagnostic index. HIF-1α may affect the development of endometriosis by regulating EMT.

Key words: Endometriosis, Hypoxia inducible factor-1α, Epithelial mesenchymal transition, Migration and invasion, Apoptosis

中图分类号:

R711.71

薛源,林雪艳,徐歌,田永杰. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 41-47.

XUE Yuan, LIN Xueyan, XU Ge, TIAN Yongjie. Expression of hypoxia-inducible factor-1α in the serum of patients with endometriosis and its effect on epithelial mesenchymal transition of eutopic endometrial stromal cells[J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 41-47.

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