子宫内膜异位症在位内膜细胞对雌二醇超敏状态的研究

Study on the over-sensitizing response of the cultured eutopic endometrial cells from endometriosis patients to estradiol

目的:观察子宫内膜异位症患者在位内膜细胞对雌二醇的反应性是否有别于正常妇女在位内膜细胞。方法:应用ELISA方法、逆转录聚合酶链式反应和流式细胞术对原代并传代培养的子宫内膜异位症患者和正常妇女的在位内膜细胞在基础状态及在雌二醇刺激后VEGF、MMP-3、MMP-9、TIMP-1和sICAM-1的分泌和(或)mRNA表达进行检测,并观察细胞增殖和凋亡状况。结果:雌二醇刺激后,子宫内膜异位症体外培养的在位内膜细胞分泌VEGF和MMP-3、表达VEGF mRNA以及细胞的增殖指数均较基础状态上调,上调的倍数分别为1.63±0.18、1.28±0.11、1.34±0.14和1.29±0.17倍,均高于对照组的1.33±0.09、1.07±0.13、1.12±0.16和1.11±0.11倍,其P值分别为0.039、0.050、0.038和0.050;子宫内膜异位症在位内膜细胞分泌TIMP-1、表达TIMP-1 mRNA、bax mRNA和凋亡指数在E2刺激后均下调,下调的倍数分别为0.51±0.07、0.66±0.15、0.73±0.08和0.76±0.09倍,均强于对照组的0.85±0.11、0.79±0.09、0.91±0.12和0.88±0.10倍,P值分别为0.043、0.050、0.038和0.029。结论:雌二醇上调内异症在位内膜细胞VEGF、MMPs的合成及增殖活性,以及其下调TIMP-1、凋亡活性的能力均强于正常内膜细胞,即子宫内膜异位症在位内膜细胞对雌二醇的刺激有一种超敏状态。

Objective：To determine the abnormal response of the cultured eutopic endometrial cells of endometriosis to estradiol. Methods： Vascular endothelial growth factor （VEGF） , matrix metalloproteinase-3 （MMP-3） ,tissue inhibitor of metalloproteinase-1 （TIMP-1） ,soluble intercellular adhesion molecule-1 （ sICAM-1 ）, VEGF mRNA, MMP-9 mRNA, TIMP-1 mRNA, bax mRNA, proliferation index （PI） and apoptosis index （ApI） in the culture media of cells and in the cells themselves no stimulated or stimulated by estradiol （E2 ） were detected by ELISA, reverse transcriptation polymerase chain reaction （RT-PCR） and flow cytometry. Results ：The ratio of up-regulation to VEGF, MMP-3 protein, VEGF, MMP-9 mRNA and PI of endometriosis eutopic endometrial cells by E2 being 1.63 ± 0.18,1.28 ± 0. 11,1.34 ±0.14 and 1.29 ± 0. 17 respectively, was stronger than that of control, being 1.33 ± 0.09,1.07 ± 0. 13, 1.12 ±0.16 and 1. 11 ±0. ll respectively,the P value was 0. 039,0. 050,0.038 and 0. 050;so did the ratio of down-regulation to T1MP-1 protein and mRNA,bax mRNA and ApI,0.51 ± 0.07,0.66 ±0.15,0.73 ±0.08 and 0.76 ±0.09 vs 0.85±0. 11,0.79 ±0.09,0.91 ±0.12 and 0.88 ＋0. IO,P value being 0. 043,0. 050,0. 038 and 0. 029. Conclusion：The cultured endometrial cells of endometriosis are more overensitizied to E2 stimulation than those cells of normal women.