2-甲氧雌二醇在早发型子痫前期患者中的表达及临床意义

The expression and clinical significances of 2-methoxyestradiol in early-onset preeclampsia

目的:研究2-甲氧雌二醇(2-ME)在早发型子痫前期患者血清中的表达及其临床意义。方法:选取孕周大于28周并且小于34周、单胎的子痫前期(PE)孕妇。其中早发型轻度PE(轻度组)25例,早发型重度PE(重度组)25例;随机选取同期单胎孕周<34周早产的健康孕妇(对照组)25例作为正常对照组。收集各组临床资料:年龄、孕周、孕产次、收缩压、舒张压、血脂、24h尿蛋白、肾功能、乳酸脱氢酶、D-二聚体等,以及期待治疗时间、新生儿出生体重及Apgar评分等,并加以统计学分析。采用酶联免疫吸附法(ELISA)检测各组孕妇血清2-ME、可溶性血管内皮生长因子受体-1(sFlt-1)、胎盘生长因子(PIGF)、内皮素-1(ET-1)水平变化;采用硝酸还原酶法测定各组孕妇血清一氧化氮(NO)含量。分析重度组血清2-ME与临床指标及sFlt-1、PIGF、ET-1、NO水平的相关性。结果:重度组孕妇血清2-ME水平(525.3±172.6)pg/ml低于对照组(705.9±157.4)pg/ml;重度组孕妇血清sFlt-1水平(5199.2±584.0)pg/ml高于轻度组(3413.4±619.7)pg/ml和对照组(2940.0±465.4)pg/ml,sFlt-1随病情加重增高明显;轻度组血清PIGF水平(81.5±17.0)pg/ml和重度组(77.4±23.5)pg/ml均低于对照组(110.2±45.0)pg/ml(P<0.01);重度组孕妇血清ET-1水平(67.6±11.2)pg/ml高于轻度组(49.7±11.0)pg/ml和对照组(32.5±7.2)pg/ml。重度组孕妇血清NO水平(48.1±9.3)μmol/L显著低于对照组(74.7±21.9)μmol/L。重度组2-ME水平与收缩压、低密度脂蛋白、甘油三脂、血浆肌酐、尿素氮和24h蛋白尿是呈负相关;与期待治疗时间呈正相关;相关系数r值分别为-0.648(P<0.01),-0.620(P<0.01),-0.649(P<0.01),-0.615(P<0.01),-0.524(P<0.01),-0.587,0.694(P<0.01)。重度组2-ME水平与sFlt-1水平呈负相关,与PIGF、NO水平呈正相关,相关系数r值分别为-0.645(P<0.01),0.511(P<0.01),0.853(P<0.01)。结论:早发型重度子痫前期组孕妇血清中2-ME水平较正常对照组降低;早发型重度子痫前期组孕妇血清中2-ME降低的水平与病情严重程度有关。

Objective:To study the expression of 2-methoxyestradiol (2-ME) in the serum of patients with early-onset preeclampsia and its correlation with the clinical severity.Methods:The pregnant women were selected with gestational weeks more than 28 weeks and less than 34 weeks, singleton pregnancy, and diagnosed as preeclampsia (PE), of which 25 cases with early-onset mild preeclampsia patients (mPE group), 25 cases with early-onset severe preeclampsia patients (sPE group); 25 cases of healthy premature birth women were randomly selected as the normal control group (NP group), who were singleton pregnancy, gestational weeks less than 34 weeks. The related clinical data were collected, including the age, gestational weeks, the history of gravidity and parity, systolic blood pressure, diastolic blood pressure, blood triglyceride,cholesterol,low density lipoprotein, 24-hour proteinuria, renal function, lactic dehydrogenase, D-dimer, treatment time, neonate birth weight, Apgar scores, etc. The pregnancy serum 2-ME, soluble vascular endothelial growth factor receptor -1 (sFlt-1), placental growth factor (PIGF) and endothelin -1 levels (ET-1) of each group were detected by enzyme linked immunosorbent assay (ELISA); the nitric oxide (NO) content of the pregnancy serum were measured by the method of nitrate reductase. The correlation between the serum 2-ME and clinical indicators and the levels of sFlt-1, PIGF, ET-1, and NO of sPE group was analyzed. Results:The 2-ME level of pregnancy serum in sPE group (525.3±172.6) pg/ml was lower than those in mPE group (645.2±177.2 ) pg/ml and NP group (705.9±157.4 ) pg/ml;The level of sFlt-1 in sPE group(5199.2±584.0)pg/ml was higher than those in mPE group(3413.4±619.7)pg/ml and NP group(2940.0±465.4)pg/ml ( P <0.05), and the increasing was obvious with the aggravation of the disease; The levels of PIGF in both mPE group(81.5±17.0)pg/ml and sPE(77.4±23.5)pg/ml were significantly lower than those in NP group(110.2±45.0)pg/ml( P <0.01); The level of ET-1 in the sPE group (67.6±11.2)pg/ml was higher than those in mPE(49.7±11.0)pg/ml and NP group(32.5±7.2)pg/ml; The level of NO in the sPE group(48.1±9.3)μmol/L was lower than those in NP group(74.7±21.9)μmol/L.There was a negative correlation between the 2-ME level and systolic blood pressure, low density lipoprotein, triglyceride, plasma creatinine, urea nitrogenand 24-hour proteinuria in sPE group; there was a positive correlation between the 2-ME level and the expectant treatment time. The correlation coefficient R values were -0.648 ( P <0.01),-0.620 ( P <0.01),-0.649 ( P <0.01),-0.615 ( P <0.01),-0.524( P <0.01),-0.587 ( P <0.01), and 0.694 ( P >0.01). There was a negative correlation between the 2-ME level and the sFlt-1 level in sPE group; there was a positive correlation between the 2-ME level and PIGF level、NO level. The correlation coefficient R values were -0.645 ( P <0.01), 0.511 ( P <0.01), 0.853 ( P <0.01). Conclusion:The serum 2-ME level of the early-onset preeclampsia pregnant women is lower than that of normal pregnant women. Low 2-ME plasma levels are associated with clinical severity indices of preeclampsia.