子宫腺肌病组织中的雌激素、雌激素受体、miR-21:致病作用和调控作用  

Estrogen,estrogen receptor and miR-21 in adenomyosis:their pathogenic roles andregulatory interactions

作　　者：曾玉燕 贾金金 卢洁 曾诚[2] 耿红玲 陈颐 ZENG Yuyan;JIA Jinjin;LU Jie;ZENG Cheng;GENG Hongling;CHEN Yi(Department of Gynecology,Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,China;Department of Gynecology,First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学第二附属医院妇科,广东广州510120 [2]广州中医药大学第一附属医院妇科,广东广州510405

出　　处：《南方医科大学学报》2024年第4期627-635,共9页Journal of Southern Medical University

基　　金：国家自然科学基金青年基金(81904233,82104913);广东省中医院朝阳人才课题(ZY2022KY04)。

摘　　要：目的探讨miR-21、雌激素(E2)及其受体(ER)在子宫腺肌病发病中的具体机制。方法采用qRT-PCR检测miR-21在子宫腺肌病组织中水平,以宫颈病变为对照组。体外原代培养子宫腺肌病细胞,qRT-PCR检测E2激活组、ICI82780(ER抑制剂)+E2激活组、E2剥夺组、E2剥夺+ER抑制组及对照组各组miR-21水平。miR-21mimic、miR-21inhibitor转染子宫腺肌病细胞,分别过表达和干扰miR-21,从正反两方面验证miR-21对子宫腺肌病细胞增殖、凋亡、迁移及细胞自噬等超微结构的影响。结果miR-21在子宫腺肌病病灶组织中的表达水平明显高于正常子宫肌层中表达水平(P<0.05),与其余各组的差异无统计学意义(P>0.05);E2激活状态下,E2激活组miR-21表达水平较ER抑制+E2激活组及对照组升高(P<0.05);E2剥夺状态下,E2剥夺+ER抑制组miR-21表达水平较E2剥夺组及对照组降低(P<0.05);干扰miR-21可以抑制子宫腺肌病细胞增殖和迁移,使线粒体内质网不同程度扩张、溶酶体增多、自噬小体出现,促进细胞的凋亡;而过表达miR-21则发挥相反的作用。结论MiR-21在子宫腺肌病细胞中通过改变细胞超微结构而发挥促增殖、迁移及抗凋亡的作用,可能与疾病的早期形成有关;ER除与E2结合调控miR-21外还可通过其他途径调控miR-21,这可能是子宫腺肌病的发病机制之一,其中ER对miR-21的调控作用大于E2。Objective To explore the pathogenic roles of miR-21,estrogen(E2),and estrogen receptor(ER)in adenomyosis.Methods We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR.In primary cultures of cells isolated from the adenomyosis lesions,the effect of ICI82780(an ER inhibitor)on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR.We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation,apoptosis,migration and autophagy of the cells.Results The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium(P<0.05).In the cells isolated from adenomyosis lesions,miR-21 expression level was significantly higher in E2 activation group than in ER inhibition+E2 activation group and the control group(P<0.05);miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group(P<0.05).The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration,expansion of mitochondrial endoplasmic reticulum,increased lysosomes,presence of autophagosomes,and increased cell apoptosis,while transfection of the cells with the miR-21 mimic produced the opposite effects.Conclusion MiR-21 plays an important role in promoting proliferation,migration,and anti-apoptosis in adenomyosis cells by altering the cell ultrastructure,which may contribute to early pathogenesis of the disease.In addition to binding with E2,ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis,thus having a stronger regulatory effect on miR-21 than E2.

关 键 词：子宫腺肌病 MIR-21 雌激素 雌激素受体 

分 类 号：R711.71[医药卫生—妇产科学]