TGF-β1和miR-21在子宫内膜异位症患者血浆中的表达及miR-21对子宫内膜间质细胞增殖和转移能力的影响  

Expression of TGF-β1 and miR-21 in plasma of patients with endometriosis and effect of miR-21 on proliferation and metastasis of endometrial stromal cells

作　　者：丁屹 袁霞 顾文文 高红艳[2] 倪息兰 林菊芳 陈继明[3] DING Yi;YUAN Xia;GU Wenwen;GAO Hongyan;NI Xilan;LIN Jufang;CHEN Jiming(Department of Obstetrics and Gynecology,People's Hospital of Jintan District,Changzhou City,Jiangsu Province,213200,China;Department of Obstetrics and Gynecology,Third Affiliated Hospital of Medical College of Suzhou University,First People's Hospital of Changzhou,Changzhou 213004,China;Department of Obstetrics and Gynecology,Changzhou Second People's Hospital Affiliated to Nanjing Medical University,Changzhou 213004,China)

机构地区：[1]江苏省常州市金坛区人民医院妇产科,江苏常州213200 [2]苏州大学医学院附属第三医院/常州市第一人民医院妇产科,江苏常州213004 [3]南京医科大学附属常州市第二人民医院妇产科,江苏常州213004

出　　处：《新疆医科大学学报》2020年第6期717-721,727,共6页Journal of Xinjiang Medical University

基　　金：常州市科技计划项目(CE20175004)。

摘　　要：目的探讨转化生长因子-β1(TGF-β1)和miR-21在子宫内膜异位症(edommometriosis,EMS)患者血浆中的表达水平,及miR-21对EMS间质细胞增殖和转移能力的影响。方法收集正常对照患者血浆30例(对照组)以及EMS患者血浆80例(EMS组),通过酶联免疫吸附实验(ELISA)检测血浆TGF-β1水平和荧光定量(PCR)法检测血浆miR-21的水平,分离培养异位子宫内膜基质细胞,并使用miR-21抑制剂对细胞内的miR-21进行干扰,通过CCK-8法和创伤愈合实验检测miR-21对子宫内膜基质细胞增殖和迁移能力的影响。结果TGF-β1在EMS组血浆中的浓度[(44.80±1.185)ng/mL]较对照组[(34.42±1.253)ng/mL]显著升高(t=4.980,P<0.0001),TGF-β1在轻度患者(I-II期)血浆中的浓度[(37.68±1.886)ng/mL]低于重度患者(III-IV期)浓度[(47.85±1.297)ng/mL];miR-21在EMS组血浆中的相对表达量(2.640±0.089)较对照组(1.332±0.098)显著升高(t=8.322,P<0.0001),miR-21在轻度患者(I-II期)血浆中的相对表达量(2.033±0.146)低于重度患者(III-IV期)表达量(2.901±0.091),EMS患者血浆miR-21与TGF-β1表达水平呈正相关(r=0.7669,P<0.01);抑制miR-21后EMS基质细胞的增殖速度和迁移能力减弱;miR-21能够抑制EMS基质细胞中Smad7的表达量。结论TGF-β1和miR-21在EMS患者血浆中表达水平较正常对照组明显升高,两者呈正相关的关系,miR-21具有促进EMS基质细胞增殖和迁移的能力,有望成为EMS的新的治疗靶点。Objective To investigate the expression of TGF-β1 and miR-21 in plasma of patients with endometriosis(EMS),and the effect of miR-21 on the proliferation and metastasis of EMS stromal cells.Methods The plasma levels of TGF-β1 in 30 normal controls and 80 EMS patients were measured by ELISA,and the levels of miR-21 in plasma were detected by fluorescence quantitative RT-PCR.Ectopic endometrial stromal cells were isolated and cultured.miR-21 inhibitors were used to interfere with miR-21 in cells.CCK-8 method and wound healing were used.The effects of miR-21 on the proliferation and migration of endometrial stromal cells were studied.Results The plasma concentration of TGF-β1 in the EMS group(44.80±1.185)ng/mL was significantly higher than that in the control group(34.42±1.253)ng/mL(P<0.0001).The plasma concentration of TGF-β1 in the mild patients(stage I-II)(37.68±1.886)ng/mL was lower than that in the severe patients(stage III-IV)(47.85±1.297)ng/mL(P<0.0001).Relative expression of miR-21 in plasma of the EMS group(2.640±0.089)was significantly higher than that of the control group(1.332±0.098)(P<0.0001).Relative expression of miR-21 in plasma of the mild patients(stage I-II)(2.033±0.146)was lower than that of the severe patients(stage III-IV)(2.901±0.091).The expression of miR-21 and TGF-β1 in plasma was positively correlated(r=0.7669,P<0.01).The proliferation rate and migration ability of EMS stromal cells in the miR-21 inhibitor group were significantly lower than those in the miR-21-NC group.MiR-21 could inhibit the expression of Smad7 in the EMS stromal cells.Conclusion The expression levels of TGF-β1 and miR-21 in plasma of the EMS patients are significantly higher than those of the control group.There is a positive correlation between them.miR-21 has the ability to promote the proliferation and migration of the EMS stromal cells,which is expected to become a new therapeutic target for EMS.

关 键 词：子宫内膜异位症 转化生长因子-Β1 MIR-21 

分 类 号：R711.71[医药卫生—妇产科学]