妊娠期高血压疾病患者胎盘组织叶酸代谢基因MTR的表达水平及其作用机制研究  

Expression Level and Effects of Folate Metabolism-related Gene MTR in Placenta of Patients with Hypertensive Disorder Complicating Pregnancy

作　　者：王维[1] 唐静[2] 杨永红[3] 薛峰 WANG Wei;TANG Jing;YANG Yong-hong;XUE Feng(Department of Laboratory Medicine,Longquanyi District Maternal and Child Health Hospital,Chengdu 610100,China;Department of Obstetrics and Gynecology,Longquanyi District Maternal and Child Health Hospital,Chengdu 610100,China;Department of Laboratory Medicine,West China Longquan Hospital,Sichuan University,Chengdu 610100,China)

机构地区：[1]成都市龙泉驿区妇幼保健院检验科,成都610100 [2]成都市龙泉驿区妇幼保健院妇产科,成都610100 [3]四川大学华西医院龙泉医院检验科,成都610100

出　　处：《现代检验医学杂志》2022年第4期134-138,173,共6页Journal of Modern Laboratory Medicine

摘　　要：目的研究叶酸代谢相关基因甲硫氨酸合成酶(methionine synthase,MTR)在妊娠期高血压疾病患者胎盘组织中的差异表达以及对于人绒毛滋养层细胞HTR8迁移及侵袭能力调控的机制研究。方法2018年1月~2020年12月在成都市龙泉驿区妇幼保健院分娩的30例妊娠期高血压,28例子痫前期和20例重度子痫前期患者及25例正常产妇作为研究对象,分娩时采集研究对象胎盘组织。使用实时荧光定量PCR(real-time quantitative PCR detecting system,qPCR)及蛋白质印迹法(western blotting,WB)检测了各组胎盘组织中MTR,上皮型钙黏附蛋白(E-Cadherin,E-Cad),锌指E盒结合蛋白-1(zinc finger E-box binding protein1,ZEB1)基因转录及蛋白表达情况。进一步通过siRNA敲减人绒毛滋养层细胞HTR8中MTR基因的表达,研究MTR对于E-Cadherin和ZEB1基因的调控作用。通过Transwell迁移及侵袭实验验证敲减MTR后对于HTR8细胞迁移和侵袭的影响。结果与对照组相比,随着妊娠期高血压疾病分期的进展,子痫前期与重度子痫前期患者胎盘组织中E-Cadherin的表达增加(1.14±0.35,1.53±0.41 vs 1.00±0.30),胎盘组织中MTR mRNA的表达量逐渐增加(1.72±0.17,2.58±0.13 vs 1.00±0.33),妊娠期高血压疾病患者胎盘组织中ZEB1的表达量下降(0.48±0.10,0.13±0.06 vs 1.00±0.22),差异具有统计学意义(F=13.28,67.1,65.41,均P<0.01)。随着疾病分期进展,MTR及E-Cadherin的蛋白表达量明显增加,而ZEB1的蛋白表达量明显降低。siRNA可以显著抑制HTR8中MTR基因mRNA的表达,敲低MTR基因后可显著抑制上皮相关标志物E-Cadherin基因mRNA的表达,可以显著促进间充质相关标志物ZEB1基因mRNA的表达,差异具有统计学意义(t=5.906,6.715,9.777,均P<0.01)。敲减HTR8细胞中MTR基因可显著促进迁移能力,侵袭实验结果显示敲减MTR基因可促进HTR8细胞的侵袭能力,差异具有统计学意义(t=6.241,22.37,均P<0.01)。结论妊娠期高血压疾病患者胎盘组织中MTR基因�Objective To study the differential expression of folate metabolism-related gene methionine synthase(MTR)in the placenta tissue of patients with pregnancy-induced hypertension and its regulation of the migration and invasion of human chorionic trophoblast cells HTR8.Methods From January 2018 to December 2020,30 cases of pregnancy-induced hypertension,28 cases of preeclampsia,20 cases of severe preeclampsia and 25 normal parturients who gave birth at the Longquanyi District Maternity and Child Health Hospital of Chengdu were the subjects of study.The placental tissue of the research subject was collected at the time.The transcription and protein expression of MTR,E-Cadherin and ZEB1 genes in each group of placental tissues were detected by qPCR and western blotting.Furthermore,siRNA was used to knock down the expression of MTR gene in human chorionic trophoblast cells HTR8 to study the regulation effect of MTR on E-Cadherin and ZEB1 genes.Transwell migration and invasion experiments were conducted to verify the effect of knocking down MTR on the migration and invasion of HTR8 cells.Results Compared with the control group,with the progress of the staging of hypertension in pregnancy,the expression of E-Cadherin(1.14±0.35,1.53±0.41 vs 1.00±0.30)in the placenta of patients with preeclampsia and severe preeclampsia increased,and the expression of MTR mRNA in the placenta tissue gradually increased(1.72±0.17,2.58±0.13 vs 1.00±0.33).Pregnancy the expression of ZEB1 in the placenta of patients with hypertensive disease decreased(0.48±0.10,0.13±0.06 vs 1.00±0.22),and the differences were statistically significant(F=13.28,67.1,65.41,all P<0.01).As the stage of the disease progressed,the protein expression of MTR and E-Cadherin increased significantly,while the protein expression of ZEB1 decreased significantly.siRNA could significantly inhibit the expression of MTR gene mRNA in HTR8.Knockdown of MTR gene could significantly inhibit the expression of epithelial-related marker E-Cadherin gene mRNA,and could signific

关 键 词：妊娠期高血压 胎盘组织 叶酸代谢 甲硫氨酸合成酶 

分 类 号：R714.246[医药卫生—妇产科学] Q786[医药卫生—临床医学]