血清血管生成素相关生长因子水平与子痫前期发病的关系

目的:探讨血清血管生成素相关生长因子(AGF)水平与子痫前期发病的关系。方法:选择2013年1月至2014年12月间在我院进行产前检查并行剖宫产终止妊娠的子痫前期患者42例作为研究组,同期收住的正常妊娠孕产妇30例作为对照组。应用双抗体酶联免疫吸附法检测血清AGF水平,应用RT-PCR法测定胎盘组织AGF mRNA水平。结果:研究组收缩压、舒张压及血清AGF水平显著高于对照组,分娩孕周显著小于对照组,新生儿出生体重显著低于对照组,差异有统计学意义(P0.05)。研究组胎盘AGF mRNA水平显著高于对照组,差异有统计学意义(P0.05)。多因素Logistic分析显示,孕产妇胎盘AGF mRNA水平与血清AGF水平、孕产妇收缩压、舒张压呈正相关(r=0.605,0.428,0.403,P均0.05)。结论:子痫前期患者血清AGF水平异常,胎盘AGF表达异常,提示AGF可能与子痫前期发病有关。     

Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy

Although a number of studies have measured circulating levels of some trace elements in preeclampsia (PE) and compared to healthy pregnant (HP), there is no consensus yet about the deficiency of some metals and development of hypertensive disorders in pregnancy. The aim of this study was to compare plasmatic levels of Zn, Mn, Co, Cu, Se and Sr among non-pregnant (NP), healthy pregnant (HP), gestational hypertensive (GH) and preeclamptic (PE) women and to correlate these levels with plasma soluble endoglin (sENG) and soluble fms-like tyrosine kinase-1 (sFLT-1), two important antiangiogenic proteins related to PE. A total of 184 women were enrolled in this study (NP = 35, GH = 51, PE = 37 and HP = 61). Trace element analyses were carried out with an inductively coupled plasma mass spectrometer (ICPMS). sENG and sFLT-1 plasma concentrations were measured by commercial ELISA kits. The most interesting result is that Sr is higher in PE (63%, P < 0.001) compared to HP and their levels are positively correlated with sENG in all three groups of pregnant women. Moreover, we found a negative correlation between Zn and sENG in HP (r = −0.43, P = 0.003). Regarding other elements, we found similar levels among pregnant groups. In conclusion, this study showed that Sr may has a role in physiopathology of PE.     

The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

BackgroundAdipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine.Material and methodsPref-1 was quantified in patients with PE (n = 51) and healthy pregnant controls (n = 51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2).ResultsIn study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 μg/l) as compared to healthy pregnant controls (0.7 μg/l) (p < 0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue.ConclusionMaternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.     

Plasma F2-isoprostane class VI isomers at 12–18 weeks of pregnancy are associated with later occurrence of preeclampsia

Preeclampsia (PE) has long been associated with early oxidative stress, although the symptoms occur later in pregnancy. We have hypothesized that the oxidative stress in PE, as characterized by the presence of F₂-isoprostane (F₂-isoP) isomers in late pregnancy, should already be present in plasma at the first regular visit of the obstetrical follow-up. There are 64 possible isomers of F₂-isoPs derived from the oxidation of arachidonic acid (AA), but only one of these isomers has been investigated so far in PE, the classical 8-iso-PGF_2α. Here, we have investigated two regioisomers of class III (8-iso-15(R)-PGF_2α and 8-iso-PGF_2α) and a mix of two isomers of class VI ((±)5-iPF_2α-VI) in plasma samples collected prospectively at 12–18 weeks from normotensive controls (n = 60) and pregnant mothers who developed PE later in pregnancy (n = 33). The plasma samples were subjected to alkaline hydrolysis followed by liquid–liquid extraction to extract total F₂-isoPs for later quantification by HPLC-MS/MS. The F₂-isoPs were normalized to either plasma volume or polyunsaturated fatty acid (PUFA) levels measured by GC-FID in plasma phospholipids. Early in pregnancy, only the class VI F₂-isoP isomers were found at concentrations significantly higher in women developing PE later in pregnancy (+13%; p = 0.0074). Normalization of F₂-isoPs to their substrate, AA, or the omega-3 to omega-6 ratio improved the predictability of PE as determined by receiver operating characteristic (from area under the curve of 0.67 to 0.68 and 0.70 respectively). Interestingly, omega-3 fatty acids were 25% higher in the control group than in the PE group (P = 0.0225). Omega-6 PUFAs correlated with F₂-Isop isomers only in cases of PE (r > 0.377; P >0.03, Spearman correlation). In sum, this study indicates that specific isomers of class VI are significant predictors of PE. This work also suggests that F₂-isoP isomers are not all generated and eliminated to the same extent and are influenced by the PUFA composition of plasma phospholipids.     

慢性高血压合并妊娠发生子痫前期的危险因素分析

目的:探讨慢性高血压合并妊娠发生子痫前期的危险因素,为筛查慢性高血压孕妇合并子痫前期提供参考依据。方法:选取2009年3月~2013年7月我院收治的慢性高血压妊娠患者116例,根据是否合并子痫前期分为慢性高血压合并妊娠组(NHDP组)和慢性高血压合并子痫前期组(HDP组),比较两组患者不同孕期的血压、尿蛋白水平以及血液生化检测指标间的差异。结果:两组间年龄、孕次、孕前尿蛋白水平、孕早期及孕中期的平均动脉压、尿蛋白水平间差异均无统计学意义(P0.05)。HDP组孕前体质指数、孕晚期的平均动脉压、尿蛋白水平、Hb、UA、LDH、FDP均较NHPD组显著升高(P0.05),两组间Plt水平差异无统计学意义(P0.05)。logistic回归分析发现Hb、UA及FDP是慢性高血压妊娠患者并发子痫前期的危险因素。结论:凝血状况、血清尿酸水平及肾功能变化是慢性高血压合并妊娠者发生子痫前期的危险因素。     

Oxidative stress and apoptosis in preeclampsia

We aimed to determine the oxidative stress and antioxidant status in preeclamptic placenta. Also, we investigated the apoptotic index of villous trophoblast and proliferation index of cytotrophoblasts. The study included 32 pregnant with preeclampsia and 31 normotensive healthy pregnant women. Malondialdehyde (MDA) and total antioxidant status (TAS) levels were measured in the placenta. For detection of apoptosis and proliferation in trophoblast, apoptosis protease activating factor 1 (APAF-1) and Ki-67 were used. Placental MDA levels in preeclamptic women were significantly higher than normal pregnancies (p = 0.002). There was no significant difference between the groups in the TAS levels of placenta (p = 0.773). Also, the apoptotic index in villous trophoblasts increased (p < 0.001), but proliferation index did not change in preeclampsia (p = 0.850). Increased oxidative stress and apoptosis in pathological placenta are not balanced by antioxidant systems and proliferation mechanisms.     

Plasma protein carbonyls in nonpregnant,healthy pregnant and preeclamptic women

Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women.

Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy non-pregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis.

Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls.

The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia.     

葡萄糖调节蛋白78在子痫前期中的表达及其意义

目的：探讨葡萄糖调节蛋白78（GRP78）mRNA及蛋白在胎盘组织的表达水平及其与子痫前期的发病关系。方法：选择2010年1月-2010年12月在南京医科大学第一附属医院江苏省人民医院产科住院的子痫前期患者35例（子痫前期组）,以同期正常孕妇35例为对照组。采用RT-PCR技术、蛋白印迹（western-blot）法和免疫组化检测两组孕妇胎盘组织中GRP78的mRNA与蛋白表达水平差异。结果：子痫前期组患者胎盘组织中GRP78mRNA与蛋白表达水平均显著高于相应孕周正常妊娠组。结论：子痫前期能够诱导GRP78表达,CHOP/GADD153表达的增高与子痫前期的发病有关。     

Expression changes of proteins associated with the development of preeclampsia in maternal plasma: A case‐control study

Defective deep placentation, involving abnormal transformation of the spiral arteries in the junctional zone of the myometrium, is known to cause significant obstetric complications, such as preeclampsia (PE), fetal growth restriction, and placental infarction leading to fetal death. Serological biomarkers to predict and diagnose PE would help antenatal care and reduce obstetric complications. To discover candidate PE biomarkers, we first performed global proteomic profiling of three pairs of plasma samples obtained from pregnant women in the early second trimester, who subsequently developed PE, and controls to identify candidate proteins that were abundant in the patients. We further evaluated the changes in the expression of PE‐representing proteins in stored plasma samples of a cohort that subsequently developed PE and their matched controls by MRM‐MS analysis. We identified that both complement C1s subcomponent (C1S) and protein AMBP were elevated in the plasma samples of the PE cohort before the manifestation of clinical disease. We propose that these proteins may be involved in the remodeling process of the spiral arteries even before PE manifestation. These proteins can serve as potential plasma biomarkers to predict the pregnant women having an increased risk of developing PE.     

Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension

We have recently developed a new target plate (BLOTCHIP^®) for MALDI‐MS. An advantage of this procedure is that it does not require the lowering of protein concentrations in test samples prior to analysis. Accordingly, this new technology enables the detection of peptides present in blood samples, including those that would otherwise be adsorbed to abundant blood proteins and would thus escape detection. Using this technology, we analyzed the peripheral blood of patients with pregnancy‐induced hypertension (PIH; the most common serious complication of pregnancy) to test a potential utility of the technology for monitoring of the pathophysiological status. In the present study, we found 23 characteristic peptides for PIH in the blood serum of pregnant women. Offline LC‐MALDI MS/MS identified 7 of the 23 peptides as fragments derived from kininogen‐1 (three peptides), fibrinogen‐α, complement component C4‐A/B, α‐2‐HS‐glycoprotein and inter‐α‐trypsin inhibitor heavy chain H4. 2‐D scatter plots with combinations of the peptides found in the present study can be grouped for pregnant women with/without PIH, which would be satisfactory reflected for their status. Additionally, the levels of most of these peptides found were significantly decreased by albumin/IgG depletion prior to BLOTCHIP^® analysis in accordance with conventional proteomics procedures. These results indicated that BLOTCHIP^® analysis can be applied for discovery study of PIH biomarker candidates.