17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞ERK1/2信号转导通路活化的影响  

Activation of Extracellular Signal-regulated Kinase1/2 Induced by 17β-estradiol in Cultured Entopic Endometrial Stromal Cells of Patient with Endometriosis

作　　者：镇澜[1] 刘义[1] 吕立群[1] 陈宏[1] 海娜[1] 廉红梅[1] 满奕村[1] 刘娜[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022

出　　处：《华中科技大学学报（医学版）》2010年第4期446-451,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30750007)

摘　　要：目的研究17β-雌二醇（17β-E2）对子宫内膜异位症（内异症）患者在位子宫内膜间质细胞胞外信号调节激酶1/2（ERK1/2）信号转导通路活化的影响,探讨ERK1/2信号转导通路在介导雌激素促进内异症发生发展中的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用1×10^-6mol/L 17β-E2处理子宫内膜间质细胞不同时间（0~120 min）,然后用MTT法和免疫印迹法（Western blot）检测子宫内膜间质细胞的活性和ERK1/2的活化情况,检测出子宫内膜间质细胞活性最强的时间点。用Western blot和MTT法分别检测不同浓度ERK1/2抑制剂PD98059对1×10^-6mol/L 17β-E2作用20 min后子宫内膜间质细胞活性及ERK1/2活性的变化。结果 1×10^-6mol/L的17β-E2作用20 min时,子宫内膜间质细胞的活性最强,ERK1/2活化在17-βE2作用10 min后出现,在20 min时达高峰;随着PD98059作用浓度的增加,ERK1/2活化水平逐渐下降,浓度为50μmol/L时已被完全阻断;随着PD98059作用浓度的增加,子宫内膜间质细胞活性逐渐下降,在50μmol/L和100μmol/L时,活性最低,但此时仍高于空白对照组。结论 17β-E2增强子宫内膜间质细胞的活性可能与17β-E2通过非转录机制,迅速激活子宫内膜间质细胞的ERK1/2信号转导通路有关。Objective To study whether extracellular signal-regulated kinasel/2（ERK1/2）signaling pathway can be activated rapidly by estrogen treatment within the cultured entopic endometrial stromal cells（ESCs）of patient with endometriosis,and the role of ERK1/2 signaling pathway in pathogenesis of endornetrJosis. Methods Entopic ESCs in patients with endometriosis were separated and cultured. The cultured cells were treated with 1×10^-6 mol/L 17β-estradiol for different durations, then the activity of ESCs was examined by MTT assay and levels of phosphorylated ERK1/2（p-ERK1/2）and total ERK1/2 were determined by Western blot. After the cultured cells were treated with 1 × 10^-6 mol/L 17β-estradiol plus PD98059 at various concentrations,selective inhibitor of ERK1/2 ,for 20 min,the activity of ESCs and levels of p-ERK1/2 and total ERK1/2 were examined by MTT assay and Western blot in the ESCs of patient with endometriosis,respectively. Results MTT assay and Western blot revealed that the activity of ESCs and the activation of PKB were increased after 10 min,and reached the peak after treatment with 1 × 10^-6 mol/L 17β-estradiol for 20 min. Levels of p ERK1/2 were decreased gradually with increased concentrations of PD98059 and 50 μmol/L PD98059 completely blocked the activation of ERK1/2 induced by 17β-estradiol. The activity of ESCs was decreased gradually with increased concentrations of PD98059, and reached the lowest when the concentrations of PD98059 were beyond 50 μmol/L. However, the activity of ESCs in the 50 μmol/L PD98059 group and the 100 μmol/L PD98059 group was still stronger than in the blank group. Conclusion It seems likely that 17β-estradiol can promptly improve activity of ESCs of patient with endometriosis by activating ERK1/2 signaling pathway through non nuclear action.

关 键 词：子宫内膜异位症 非转录途径 17Β-雌二醇 ERK1/2信号转导通路 

分 类 号：R711.71[医药卫生—妇产科学]