miR-125b在早发型重度子痫前期中对白细胞介素-8的调控研究  

Regulation of miR-125b on interleukin-8 in early-onset severe preeclampsia

作　　者：刘梦婷 杨潍潍 张翠娟[3] 李清华[4] 李洁[3] 

机构地区：[1]潍坊医学院临床医学院,山东潍坊261053 [2]潍坊医学院药学与生物科学学院细胞生物学教研室,山东潍坊261053 [3]潍坊医学院附属医院产科,山东潍坊261053 [4]潍坊医学院公共卫生学院预防实验室,山东潍坊261053

出　　处：《中国计划生育和妇产科》2017年第12期30-35,共6页Chinese Journal of Family Planning & Gynecotokology

基　　金：国家自然科学基金(项目编号:81601318);山东省自然科学基金项目资助(项目编号:ZR2015HL021)

摘　　要：目的研究白细胞介素-8(interleukin-8,IL-8)在早发型重度子痫前期(early-onset severe pre-eclampsia,EOSP)患者中的表达水平及miR-125 b对其的调控作用。方法选取2014年1月至2015年7月在潍坊医学院附属医院及潍坊市妇幼保健院行剖宫产分娩且按照威廉姆斯产科学诊断为EOSP的产妇17例为EOSP组,随机选取同期无任何孕期并发症的正常产妇40例为对照组。通过定量聚合酶链反应检测EOSP患者及正常产妇胎盘中miR-125 b及IL-8的表达水平;用miR-125 b模拟物、miR-125 b抑制剂及其相应的空白对照分别转染人绒毛膜滋养层细胞株;荧光素酶试验进一步验证鞘氨醇-1-磷酸受体(sphingosine-1-phosphate lyase 1,SGPL 1)是否为miR-125 b的靶基因;用酶联免疫吸附试验确定细胞培养物上清液中的IL-8浓度。结果研究发现miR-125 b和IL-8在EOSP组患者的胎盘组织中失调,说明miRNA与IL-8在EOSP中有潜在联系。EOSP患者胎盘中miR-125 b与SGPL1负相关,过表达miR-125 b可以显著降低SGPL 1的表达,且荧光素酶试验表明SGPL 1是miR-125 b的直接靶标;miR-125 b通过直接靶向SGPL 1来增加IL-8产生,并且这种效应可以被SGPL 1的过表达逆转。结论 miR-125 b在EOSP的发展过程中调节IL-8,miR-125 b和SGPL 1可能成为EOSP潜在的临床预测和治疗的靶标。Objective To investigate the expression of interleukin - 8 （ IL - 8 ） in early - onset severe pre - eclampsia （EOSP） and its regulation by miR - 125b. Methods 57 pregnant women who had the cesarean section at Weifang Affiliated Hospital of Medical College and Weifang Maternal and Child Health Hospital from January 2014 to July 2015 were selected, and 17 of them diagnosed as EOSP according to Williams Obstetrics were selected as the EOSP group, the other 40 without any complications were selected as the control group. The control group were selected in random during the corresponding period. The levels of miR - 125b and IL - 8 in the placenta of EOSP patients and normal pregnant women were detected by quantitative polymerase chain reaction. Human chorionic trophoblast cell lines were transfected with miR - 125b mimics, miR - 125b inhibitor and its corresponding blank control, respectively. Luciferase assay further confirmed whether sphingosine - 1 - phosphate lyase 1 （ SGPL 1 ） was the target gene of miR - 125b; IL - 8 concentrations in cell culture supematants were determined by enzyme - linked immunosorbent assay （ELISA）. Results The study found that miR - 125b and IL - 8 in placental tissue disorder in EOSP patients, indicating that miRNA and IL - 8 in EOSP were potentially linked. MiR - 125b was negatively correlated with SGPL 1 in placenta of EOSP patients, and over - expression of miR - 125b could significantly reduce SGPL 1 expression. Luciferase assay showed that SGPL 1 was the direct target of miR - 125b. MiR - 125b increased IL- 8 production by targeting SGPL 1 directly, and this effect can be reversed by SGPL 1 overexpression. Conclusion MiR - 125b regulates IL - 8 during the development of EOSP, and miR - 125b and SGPL 1 may be potential targets for clinical prediction and treatment of EOSP.

关 键 词：miR-125 b EOSP IL-8 SGPL 1 滋养层 

分 类 号：R714.24[医药卫生—妇产科学]