早期妊娠丢失患者蜕膜组织中血管重塑相关miRNA及其靶基因表达的研究  

Expression of miRNA and target genes related to vascular remodeling in deciduas of early pregnancy loss

作　　者：俞田田 洪丽华[2] 张颖[1] 陆海茜 范建霞[1] YU Tiantian;HONG Lihua;ZHANG Ying;LU Haiqian;FAN Jianxia(Department of Obstetrics,the International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University(The International Peace Maternity and Child Health Hospital of China Welfare Institute),Shanghai Key Laboratory of Embryo Original Diseases,Shanghai 200030,China;不详)

机构地区：[1]上海交通大学医学院附属国际和平妇幼保健院(中国福利会国际和平妇幼保健院)产科,上海市胚胎源性疾病重点实验室,200030 [2]浙江大学医学院附属妇产科医院妇科

出　　处：《浙江医学》2023年第22期2374-2379,共6页Zhejiang Medical Journal

基　　金：国家重点研发计划项目(2018YFC1004602)。

摘　　要：目的探讨早期妊娠丢失(EPL)患者蜕膜组织中血管重塑相关miRNA及其靶基因的表达。方法选取2020年10至12月在上海交通大学医学院附属国际和平妇幼保健院门诊手术室行早孕人工流产手术的患者40例为研究对象,其中因EPL行人工流产手术者20例(EPL组),正常早孕要求终止妊娠行人工流产者20例(对照组),收集其废弃的流产蜕膜组织。采用q RTPCR法检测两组患者蜕膜组织中与血管重塑相关的差异表达miRNA。通过3’非翻译区(3’-UTR)荧光素酶报告基因验证miRNA与其预测靶基因之间的关系。qRT-PCR和Western blot法验证两组患者蜕膜组织中预测靶基因的表达。结果EPL组患者蜕膜组织中miR-29c-3p、miR-193a-5p和miR-125a-5p表达水平均升高,而其对应的靶基因血管内皮生长因子A(VEGFA)和基质金属蛋白酶2(MMP-2)mRNA和蛋白表达水平均下调。3’-UTR荧光素酶报告基因证实差异表达的miRNA与预测靶基因之间存在负调控。结论蜕膜组织中miR-29c-3p、miR-125a-5p、miR-193a-5p可能通过下调靶基因VEGFA和MMP-2参与EPL发生、发展,本研究提供了研究早期自然流产的新方向,但确切机制需进一步深入研究。Objective To verify the expression of miRNA and target genes associated with vascular remodeling in deciduas of patients with early pregnancy loss(EPL).Methods From October 2020 to December 2020,this study enrolled 40 participants with early pregnancy who induced abortion in the outpatient operating room of the International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University,20 with normal early pregnancy(control group)and 20 with EPL(EPL group),and collected their deciduas.Differentially expressed miRNA associated with vascular remodeling in deciduas of both groups were detected with quantitative real-time polymerase chain reaction(qRTPCR).The relationship between miRNA and the predicted target genes were verified by 3'-untranslated region(3'-UTR)luciferase reporter assays.The expressions of those target genes in deciduas were detected from both control and EPL groups by qRT-PCR and Western blot.Results The expressions of miR-125a-5p,miR-29c-3p,and miR-193a-5p were up-regulated in deciduas of EPL group,whereas the mRNA and protein expressions of target genes of vascular endothelial growth factor A(VEGFA)and matrix metalloproteinase 2(MMP-2)were down-regulated.The negative regulatory relationship between differentially expressed miRNA and predictive target genes was confirmed by 3'-UTR luciferase reporter assays.Conclusion The up-regulation of miR-29c-3p,miR-125a-5p,and miR-193a-5p in deciduas may contribute to EPL occurrence and development by down-regulating the target genes of VEGFA and MMP-2.This study provides a new direction for the study of EPL,but the exact mechanism needs further study.

关 键 词：早期妊娠丢失 血管重塑 微小RNA 血管内皮生长因子A 基质金属蛋白酶2 

分 类 号：R714[医药卫生—妇产科学]