Abstract:

Objective　To investigate the expressions of circular RNA DLG1 (circDLG1), hypoxia-inducible factor-1α (HIF-1α), placental growth factor (PLGF), and placental microvascular density (MVD) in placental tissue of patients with pre-eclampsia (PE) and their relationship. Methods　A total of 116 pregnant women with PE who delivered in Department of Obstetrics, The Second Affiliated Hospital of Xi'an Medical University from January 2020 to December 2023 were selected as an observation group; they were (29.15±5.82) years old; there were 72 primiparas, and 44 multiparas; their gestational age was (37.02±2.14) weeks. A total of 116 healthy pregnant women in the same period were selected as a control group; they were (28.72±5.36) years old; there were 78 primiparas and 38 multiparas; their gestational age was (36.68±2.02) weeks. The clinical data, including age, BMI before pregnancy and at delivery, parity, gestational week, diastolic and systolic blood pressures, blood urea nitrogen, lactate dehydrogenase (LDH), creatinine (Cr), urea protein, platelet count (PLT), mean platelet volume (MPV), albumin (ALB), total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), in both groups were collected. The real time quantitative-polymerase chain reaction (qRT-PCR) was used to measure the expressions of circDLG1, HIF-1α, and PLGF in the two groups, and the MVD was calculated. The factors influencing PE were analyzed by the multivariate logistic regression analysis. Results　The systolic and diastolic blood pressures and levels of BUN, LDH, Cr, and urinary protein in the observation group were higher than those in the control group, and the levels of MPV and ALB were lower (all P<0.05). There were no statistical differences in age, BMI before pregnancy and at delivery, parity, gestational week, and levels of PLT, TBIL, ALT, and AST between the two groups (all P>0.05). The results of qRT-PCR showed that the HIF-1α mRNA level in the observation group was higher than that in the control group (0.64±0.15 vs. 0.47±0.11, P<0.05), and the expression level of circDLG1 mRNA (0.62±0.24 vs. 1.08±0.47), PLGF mRNA level (1.12±0.18 vs. 1.68±0.23), and MVD count, (45.26±6.58 vs. 75.26±8.11) were lower (all P<0.05). The relative expression of circDLG1 in the patients was negatively correlated with HIF-1α (r=-0.564; P<0.05), and positively with PLGF and MVD (r=0.547 and 0.621; both P<0.05). The logistic regression analysis showed that LDH, urinary protein, and MPV were independent risk factors for PE (all P<0.05), and the high circDLG1, PLGF, and MVD levels and a low HIF-1α level were independent protective factors for PE (all P<0.05). Conclusions　In the placental tissue of patients with PE, the expression levels of circDLG1, HIF-1α, and MVD are low, while the expression level of PLGF is high; the relative expression level of circDLG1 is closely related to HIF-1α, PLGF, and MVD; high levels of circDLG1, PLGF, and MVD and a low level of HIF-1α are independent protective factors for the occurrence of PE.

Key words: Pre-eclampsia,  , Placenta,  , Circular RNA DLG1,  , Hypoxia-inducible factor-1α,  , Placental growth factor,  , Microvessel density

摘要：

目的　研究子痫前期（PE）孕妇胎盘组织中环状RNA DLG1（circDLG1）与缺氧诱导因子-1α（HIF-1α）、胎盘生长因子（PLGF）、胎盘组织微血管密度（MVD）的表达情况及相互关系。方法　采用前瞻性研究，选取2020年1月至2023年12月于西安医学院第二附属医院妇产科分娩的116例PE孕妇为观察组，年龄（29.15±5.82）岁，初产72例、经产44例，孕周（37.02±2.14）周。另选取同期116例产前检查健康的孕妇为对照组，年龄（28.72±5.36）岁，初产78例、经产38例，孕周（36.68±2.02）周。收集两组孕妇的临床特征：年龄、孕前和分娩时BMI、产次、孕周、收缩压、舒张压、尿素氮（BUN）、乳酸脱氢酶（LDH）、肌酐（Cr）、尿蛋白、血小板计数（PLT）、平均血小板体积（MPV）、白蛋白（ALB）、总胆红素（TBIL）、丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST），采用实时定量-聚合酶链式反应（qRT-PCR）检测两组胎盘组织中circDLG1、HIF-1α及PLGF表达情况，并计数MVD。组间统计比较行t检验、χ2检验，Pearson相关系数法分析PE患者胎盘组织中circDLG1与HIF-1α、PLGF及MVD的相关性，采用多因素logistic回归分析PE的影响因素。结果　观察组孕妇的收缩压、舒张压、BUN、LDH、Cr及尿蛋白均高于对照组（均P<0.05），MPV和ALB均低于对照组（均P<0.05）；两组孕妇在年龄、孕前和分娩时BMI、产次、孕周、PLT、TBIL、ALT及AST等比较，差异均无统计学意义（均P>0.05）。qRT-PCR结果显示，观察组孕妇胎盘组织中的HIF-1α mRNA水平高于对照组（0.64±0.15比0.47±0.11，P<0.05），circDLG1 mRNA、PLGF mRNA、MVD计数均低于对照组（0.62±0.24比1.08±0.47、1.12±0.18比1.68±0.23，45.26±6.58比75.26±8.11，均P<0.05）。且PE患者胎盘组织中的circDLG1相对表达量与HIF-1α呈负相关（r=-0.564，P<0.05），与PLGF及MVD呈正相关（r=0.547、0.621，均P<0.05）。Logistic回归分析结果显示，LDH、尿蛋白、MPV均是PE发生的独立危险因素（均P<0.05），高水平circDLG1、PLGF、MVD及低水平HIF-1α是PE发生的独立保护因素（均P<0.05）。结论　PE患者胎盘组织中circDLG1、HIF-1α及MVD表达水平较低，PLGF表达水平较高，且circDLG1相对表达量与HIF-1α、PLGF及MVD密切相关，同时高水平circDLG1、PLGF、MVD及低水平HIF-1α是PE发生的独立保护因素。

关键词: 子痫前期,  ,  , 胎盘,  ,  , 环状RNA DLG1,  ,  , 缺氧诱导因子-1α,  ,  , 胎盘生长因子,  ,  , 微血管密度