miR-19a在正常妊娠及重度子痫前期患者胎盘中的表达

目的：通过检测正常妊娠及重度子痫前期患者胎盘组织中miR-19a的表达,探讨其与子痫前期发病的关系。方法：收集10例重度子痫前期患者胎盘组织（实验组）和10例正常产妇胎盘组织（对照组）,应用荧光实时定量PCR（Real Time PCR）的方法检测两组miR-19a的表达差异。结果：重度子痫前期患者胎盘组织中miR-19a表达升高（P〈0.05）。结论：子痫前期患者胎盘组织中存在差异表达的miRNA,miR-19a在胎盘组织中的高表达可能与子痫前期的发病有关。     

Thrombin impairs the angiogenic activity of extravillous trophoblast cells via monocyte chemotactic protein-1 (MCP-1): A possible link with preeclampsia

Cytokines’ secretion from the decidua and trophoblast cells has been known to regulate trophoblast cell functions, such as Extravillous trophoblasts (EVTs) cell migration and invasion and remodeling of spiral arteries. Defective angiogenesis and spiral arteries transformation are mainly caused by proinflammatory cytokines and excessive thrombin generation during preeclampsia. Monocyte chemotactic protein-1 (MCP-1), a crucial cytokine, has a role in maintaining normal pregnancy. In this study, we explored whether thrombin regulates the secretion of MCP-1 in HTR-8/SVneo cells; if yes, what is its function? We used HTR-8/SVneo cells, developed from ?rst trimester villous explants of early pregnancy, as the model of EVTs. MCP-1 gene silencing was performed using gene-specific siRNA. qPCR and ELISA were performed to estimate the expression and secretion of MCP-1. Here, we found that thrombin enhanced the secretion of MCP-1 in HTR-8/SVneo cells. Proteinase-activated receptor-1 (PAR-1) was found as the primary receptor, regulating MCP-1 secretion in these cells. Furthermore, MCP-1 secretion is modulated via protein kinase C (PKC) α, β, and Rho/Rho-kinase-dependent pathways. Thrombin negatively regulates HTR-8/SVneo cells’ ability to mimic tube formation in an MCP-1 dependent manner. In conclusion, we propose that thrombin-controlled MCP-1 secretion may play an essential role in normal placental development and successful pregnancy maintenance. Improper thrombin production and MCP-1 secretion during pregnancy might cause inadequate vascular formation and transformation of spiral arteries, which may contribute to pregnancy disorders, such as preeclampsia.     

低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响

目的:研究低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响。方法:将90只孕期大鼠以随机数表法分成正常孕组、子痫前期组、治疗组,每组30只。其中子痫前期组和治疗组大鼠于妊娠第13 d开始皮下注射左旋硝基精氨酸甲酯,建立子痫前期大鼠模型,注射剂量为200 mg/(kg·d),正常孕组予以等量生理盐水注射干预。治疗组予以低分子肝素皮下注射干预,注射剂量为40μL/(kg·d),子痫前期组以及正常孕组大鼠予以同等剂量的生理盐水注射处理。比较三组大鼠的血压、24 h蛋白尿,肝功能指标水平,血清炎症因子水平,胎盘组织中Bcl-2及Bax蛋白表达水平。结果:子痫前期组及治疗组大鼠妊娠第15 d、21 d时的血压水平均显著高于正常孕组,且妊娠第21 d时的24 h蛋白尿高于正常孕组,治疗组大鼠妊娠第21 d的血压及24 h蛋白尿均低于子痫前期组(均P<0.05)。妊娠第21 d时子痫前期组、治疗组大鼠的谷丙转氨酶(ALT)、谷草转氨酶(AST)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、γ-干扰素(IFN-γ)水平均显著高于正常孕组,且治疗组低于子痫前期组(均P<0.05)。子痫前期组、治疗组大鼠胎盘组织中Bcl-2蛋白表达水平显著低于正常孕组,Bax蛋白表达水平显著高于正常孕组,且治疗组大鼠Bcl-2蛋白表达水平显著高于子痫前期组,Bax蛋白表达水平显著低于子痫前期组(均P<0.05)。结论:低分子肝素对子痫前期大鼠中具有明显的降血压效果,有利于改善大鼠肝功能,其主要作用机制可能与诱导Th1/Th2的平衡朝Th2方向发展,调节Bcl-2/Bax平衡有关。     

Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues

The placenta is important in providing a healthy environment for the fetus and plays a central role in the pathophysiology of preeclampsia (PE). Fetal and placental developments are influenced by epigenetic programming. There is some evidence that PE is controlled to an altered circadian homeostasis. In a nested case–control study embedded in the Rotterdam Periconceptional Cohort, we obtained placental tissue, umbilical cord leukocytes (UCL), and human umbilical venous endothelial cells of 13 early-onset PE, 16 late-onset PE and 83 controls comprising 36 uncomplicated and 47 complicated pregnancies, i.e. 27 fetal growth restricted and 20 spontaneous preterm birth. To investigate the associations between PE and the epigenetics of circadian clock and clock-controlled genes in placental and newborn tissues, genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation450K BeadChip and a candidate-gene approach using ANCOVA was applied on 939 CpGs of 39 circadian clock and clock-controlled genes. DNA methylation significantly differed in early-onset PE compared with spontaneous preterm birth at 6 CpGs in placental tissue (3.73^E-5 ≤ p ≤ 0.016) and at 21 CpGs in UCL (1.09^E-5≤ p ≤ 0.024). In early-onset PE compared with fetal growth restriction 2 CpGs in placental tissue (p < 0.05) and 8 CpGs in uncomplicated controls (4.78^E-5≤ p ≤ 0.049) were significantly different. Moreover, significantly different DNA methylation in early-onset PE compared with uncomplicated controls was shown at 6 CpGs in placental tissue (1.36^E-4≤ p ≤ 0.045) and 11 CpGs in uncomplicated controls (2.52^E-6≤ p ≤ 0.009). No significant associations were shown with late-onset PE between study groups or tissues. The most differentially methylated CpGs showed hypomethylation in placental tissue and hypermethylation in uncomplicated controls. In conclusion, DNA methylation of circadian clock and clock-controlled genes demonstrated most differences in UCL of early-onset PE compared with spontaneous preterm birth. Implications of the tissue-specific variations in epigenetic programming for circadian performance and long-term health need further investigation.     

BMP-7 在子痫前期肾脏损伤中的表达及临床意义

目的：探究BMP-7 在子痫前期肾脏损伤中的表达及临床意义。方法：选取2012 年3 月到2013 年12 月我院妇产科收治的98 例子痫前期肾脏损伤患者作为研究对象,以30例健康孕妇为对照,分别采用ELISA 方法检测血液、尿液中BMP-7 蛋白、尿茁2微 球蛋白（beta2-MG）浓度,以苄索氯胺比浊法测定24 h尿蛋白定量。结果：①与对照组相比,子痫前期肾脏损伤患者尿液及血清 BMP-7 蛋白浓度显著降低(P<0.05);②随着病程进展,子痫前期组尿液血清BMP-7 蛋白浓度、尿白蛋白定量、beta2-MG 显著升高 (P<0.05);③子痫前期组尿液、血清BMP-7 蛋白浓度分别与尿白蛋白定量、beta2-MG 成正相关（P＜0.05）。结论：子痫前期肾脏损伤 患者血清BMP-7 蛋白水平显著降低,可用于评估子痫前期肾脏损伤进展,对临床具有指导意义。     

肿瘤坏死因子alpha与子痫前期的关系

子痫前期是妊娠期特有疾病,是导致孕产妇及围生儿病死率的重要原因,其病因和发病机理仍未完全明确。目前,已被提出 和子痫前期的发生相关的因素包括遗传、氧化应激、异常滋养层细胞侵入、血管内皮细胞功能紊乱、营养缺乏、免疫缺陷等,其中 内皮细胞损伤导致的内皮细胞生理功能紊乱已经成为子痫前期病因学研究的热点。肿瘤坏死因子-alpha(tumor necrosis factor-alpha, TNF-alpha)在内皮细胞损害中发挥着重要作用,可能通过诱导炎性因子和血管内皮细胞黏附分子-1(VCAM-1)生成、抑制基质金属蛋 白酶(MMP)、影响血管活性物质、脂联素、瘦素和血管因子生成,介导子痫前期的发生。本文就TNF-琢与子痫前期发生的关系进行 综述。     

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。     

Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia

Preeclampsia (PE) is the leading cause of maternal deaths in primipara. It is mainly characterized by defect migration and invasion of trophoblast cells. Circular RNAs (circRNAs) have been widely reported to be associated with PE progression. This study is designed to explore the role and mechanism of circ_0032962 on trophoblast cell behavior. Circ_0032962, microRNA-326 (miR-326), and Pre-B-cell leukemia homeobox 3 (PBX3) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability, migration, and invasion were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), Colony formation, wound healing, and transwell assays. Protein levels of E-cadherin, Vimentin, N-cadherin, and PBX3 were examined by western blot assay. The binding relationship between miR-326 and circ_0032962 or PBX3 was predicted by circular RNA Interactome or Starbase and then verified by a dual-luciferase reporter assay. Circ_0032962 and PBX3 levels were declined in placenta tissues from preeclampsia patients, and miR-326 was elevated. Apart from that, circ_0032962 knockdown could suppress cell proliferation ability, migration, invasion, and epithelial-mesenchymal transition (EMT) in trophoblast cells. Mechanically, circ_0032962 could affect PBX3 expression through sponging miR-326. Circ_0032962 could contribute to trophoblast cell growth ability and metastasis partly by regulating the miR-326/PBX3 axis, providing a novel insight into the pathogenesis and treatment of PE.     

硫酸镁联合小剂量阿司匹林治疗子痫前期效果及子宫动脉血流、胎盘VEGF、MMP-9表达影响研究

摘要 目的：探讨硫酸镁联合小剂量阿司匹林治疗子痫前期效果及子宫动脉血流、胎盘血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）表达影响研究。方法：选择2019年6月-2021年1月在我院接受治疗的125例子痫前期患者,采用随机数表法分为试验组（n=63）和对照组（n=62）。对照组给硫酸镁治疗,试验组在对照组的基础上联合小剂量阿司匹林治疗。比较两组临床疗效、子宫动脉血流、胎盘VEGF、MMP-9、血压水平变化情况及妊娠不良结局发生情况。结果：治疗后,两组总有效率比较差异显著（P<0.05）;治疗前,试验组和对照组子宫动脉指标水平比较无显著差异;治疗后,试验组和对照组RI、PI及S/D水平均随着时间的推移而升高,且试验组均高于对照组,差异显著（P<0.05）;治疗前,试验组和对照组胎盘VEGF、MMP-9水平比较无显著差异;治疗后,试验组和对照组胎盘VEGF、MMP-9水平均随着时间的推移而升高,且试验组均高于对照组,差异显著（P<0.05）;治疗前,试验组和对照组血压水平比较无显著差异;治疗后,试验组和对照组血压水平均随着时间的推移而降低,且试验组均低于对照组,差异显著（P<0.05）;试验组胎儿窘迫、宫缩乏力及新生儿窒息发生率均显著低于对照组,差异显著（P<0.05）。结论：在子痫前期中应用硫酸镁联合小剂量阿司匹林治疗疗效显著,可有效改善患者子宫动脉血流、胎盘VEGF、MMP-9水平。