RhoA在子痫前期患者胎盘中的表达

目的:检测正常晚期妊娠和子痫前期患者胎盘RhoA的表达,探讨RhoA在子痫前期发病中的作用。方法:用免疫组织化学SP法及RT-PCR检测40例子痫前期和20例正常晚期妊娠胎盘RhoA蛋白及其mRNA的表达。结果:RhoA主要在滋养细胞表达。轻度子痫前期组和重度子痫前期组RhoA蛋白及mRNA均高于正常晚期妊娠组,差异有统计学意义(P<0.05)。结论:子痫前期患者胎盘RhoA的高表达可能与子痫前期的发病有一定的关系。     

子痫前期胎盘学研究进展

子痫前期是一种妊娠期特有疾病,以高血压和蛋白尿为临床特征,可伴有全身多脏器损伤.由于其病因不明,除终止妊娠之外缺乏有效的临床治疗方法,始终是引起孕产妇死亡的主要原因之一.目前,子痫前期发病机制的"两阶段"理论已经得到普遍认同,即:第1阶段为胎盘形成的早期,滋养细胞对子宫内膜侵入过浅,子宫螺旋小动脉重铸障碍,导致胎盘"浅着床",是子痫前期发病的始动因素.     

子痫前期胎盘因素在胎儿生长受限中的作用

胎儿生长受限(FGR)为子痫前期最常见的并发症,子痫前期和胎儿生长受限的发病基础有共同之处,与胎盘浅着床代偿性分泌一系列异常活性因子有关,并引发胎盘功能不良、胎儿生长受限等妊娠不良结局。近年许多实验着力于进一步研究子痫前期血管生长因子、胎盘内分泌激素及细胞因子的表达差异与FGR发生的相关性,为子痫前期的病情发展及预测妊娠结局和治疗提供新的依据。     

胎盘生长因子与子痫前期发病及一氧化氮关系的研究

目的:探讨胎盘生长因子(PLGF)在子痫前期发病中的作用及其与一氧化氮的关系。方法:选择妊娠期高血压疾病患者45例,其中妊娠期高血压10例,轻度子痫前期12例,重度23例;选择同期正常妊娠妇女20例作为对照组。采用免疫组织化学染色法和逆转录-聚合酶链式反应(RT-PCR)检测两组患者胎盘PLGF蛋白及mRNA的表达。采用硝酸盐还原酶法测定两组胎盘组织NO浓度的变化。结果:(1)免疫组化结果显示,轻度和重度子痫前期的胎盘绒毛合体滋养细胞、绒毛间质PLGF表达均显著低于正常妊娠组(P<0.05),妊娠期高血压组与正常组无差别;PLGF在妊娠期高血压、子痫前期组及正常妊娠组分布范围基本一致,主要分布在绒毛合体滋养细胞和间质细胞胞浆,部分血管合体膜上也有表达;(2)轻、重度子痫前期胎盘组织PLGF mRNA平均灰度分别为3.33±0.39、1.97±0.29,显著低于正常妊娠组的平均灰度4.87±0.60(P<0.01);(3)轻、重度子痫前期胎盘组织中NO浓度分别为8.20±5.56μmol/g、6.46±2.25μmol/g,显著低于对照组18.10±7.12μmol/g(P<0.05);妊娠期高血压组胎盘组织NO浓度与对照组差异无显著性;(4)胎盘组织中胎盘生长因子表达水平与胎盘组织NO浓度呈显著正相关(r=0.54,P<0.05)。结论:子痫前期胎盘组织中胎盘生长因子水平降低,NO浓度下降,可能在子痫前期的发病中起一定作用。     

Smad4在早发型子痫前期胎盘组织中的表达及意义

Objective?To investigate the expression of Smad4 in placental tissue of early onset preeclampsia and its possible role. Method?Smad4 expression was detected by RT-PCR, Western blot and immunohistochemistry in placental tissues of 30 cases of early onset preeclampsia and 30 healthy parturients. Transwell and scratch assay were used to detect the invasion and migration of trophoblast cell line HTR-8/SVneo cells. Result?Smad4 mRNA and protein levels in placental tissues of early onset preeclampsia were significantly increased (P<0.01); Compared with the si-Smad4 NC group, the invasion and mobility of HTR-8/SVneo cells were significantly increased after Smad4 silencing, and the difference was statistically significant (P<0.01). Conclusion?Smad4 expression is significantly increased in placental tissue of early onset preeclampsia, which may be involved in the occurrence and development of preeclampsia by affecting the biological function of trophoblast cells.     

早发型子痫前期胎盘细胞侵袭相关信号通路表达及其交互作用的研究

目的：探讨细胞侵袭相关Notch1及Wnt1信号通路在早发型子痫前期患者胎盘组织中的表达以及两者的交互作用。方法：收集2016年6月—2017年12月郑州人民医院收治的176例早发型子痫前期患者（轻度组102例、重度组74例），同期60例健康孕妇为对照组。收集所有研究对象分娩后的胎盘组织样本，通过免疫组织化学法检测组织Notch1及Wnt1蛋白的表达，Western blotting检测Notch1、Jagged1、Wnt1及β-catenin蛋白表达水平，并对各蛋白表达水平进行相关性分析。结果：3组Notch1及Wnt1表达强度和阳性表达率差异均有统计学意义（P＜0.05）；轻度组和重度组Notch1及Wnt1阳性表达率低于对照组，重度组阳性表达率低于轻度组（P＜0.05）。3组Notch1、Jagged1、Wnt1及β-catenin蛋白表达水平差异有统计学意义（P＜0.05）；轻度组及重度组Notch1、Jagged1及Wnt1蛋白表达水平均低于对照组，重度组β-catenin表达水平低于对照组，且重度组Notch1、Jagged1及Wnt1及β-catenin均低于轻度组（均P＜0.05）。Notch1与Jagged1（r=0.826，P=0.000）、Wnt1与β-catenin（r=0.531，P=0.000）表达水平呈正相关，Wnt1与Notch1（r=－0.167，P=0.010）、Wnt1与Jagged1（r=－0.136，P=0.037）表达水平呈负相关。结论：Notch1及Wnt1低表达与早发型子痫前期的发生、发展相关，且在该过程中Notch及Wnt信号通路之间可能存在一定的交互作用。     

胎盘微环境改变与子痫前期

胎盘对于胎儿发育至关重要,胎儿血与母体血在胎盘单位内进行养分交换。子痫前期发病的关键环节即为滋养细胞浸润不足引起的对子宫螺旋动脉重塑障碍。可溶性血管内皮生长因子受体-1与胎盘生长因子的比值在子痫前期的发病、诊断及不良妊娠结局的发生率中可能有重要预测价值。     

胎盘印迹基因在子痫前期发病中的作用研究进展

<正>子痫前期（preeclampsia,PE）是妊娠期特有并发症,是导致孕产妇和围产儿死亡的主要原因之一,其发病机制至今仍未阐明。目前的研究主要集中于滋养细胞功能异常、氧化应激、血管内皮细胞损伤、免疫学因素和遗传因素等方面。随着表观遗传学的研究进展,发现胎盘印迹基因的异常表达可导致滋养细胞功能异常、促进氧化应激损伤和血管内皮细胞损伤,参与子痫前期的发生。本文就胎盘印迹基因与子痫前期发生的可能机制综述如下。     

survivin和livin在子痫前期胎盘中的表达及意义

目的:检测抑凋亡基因survivin和livin在子痫前期患者胎盘的表达,研究滋养细胞凋亡与子痫前期的关系。方法:用免疫组化SP法检测胎盘组织中survivin和livin的表达,其中子痫前期20例、子痫4例、正常晚期妊娠20例,用计算机图像分析系统定量分析。结果:(1)survivin主要位于绒毛小叶的合体滋养细胞及细胞滋养细胞,在子痫前期的表达显著低于正常晚期妊娠(P<0.05),随病情加重表达降低;(2)livin主要在合体滋养细胞的细胞核中表达,在子痫前期、子痫组的表达均低于正常晚期妊娠(P<0.05);(3)子痫前期、子痫中survivin和livin表达无相关性(P>0.05)。结论:子痫前期及子痫患者胎盘组织中survivin、livin的表达均明显低于正常对照组,但两者无相关性(r=0.142,P=0.298,P>0.05)。     

雌激素受体信号通路与子痫前期的关系

子痫前期（pre-eclampsia,PE）是一种以高血压和多系统器官功能受累为特征的妊娠特异性综合征,虽然其具体发病机制尚不明确,但胎盘形成时期滋养细胞侵袭过浅或受限而导致的胎盘灌注不足、持续缺氧可能是重要的初始事件。作为胎盘分泌的重要类固醇激素,雌激素通过雌激素受体（estrogen receptor,ER）、雌激素反应元件（estrogen response element,ERE）信号通路的基因组或非基因组效应调控靶基因表达水平,致使滋养细胞增殖、凋亡和侵袭等生物学行为发生改变,还可能介导子宫内膜蜕膜化缺失从而参与胎盘浅着床、灌注不足的发生。雌激素及其信号通路还可通过调节一氧化氮等血管活性因子水平及有关离子通道活性,调节子宫动脉平滑肌的舒缩能力,通过多种机制参与PE、复发性流产等高危妊娠的发生和发展。     

mTOR信号通路与子痫前期发病的相关性

子痫前期（preeclampsia,PE）是临床常见的妊娠期特发性疾病,其病情变化呈动态性进展,临床表现多样化,病因机制迄今尚未完全阐明,主要认为与遗传因素、免疫因素、营养因素和环境因素等密切相关。近年有研究表明,哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）信号通路通过调控细胞增殖、侵袭、迁移和凋亡能力,参与胎盘滋养细胞与血管内皮细胞活性的调节,且胰岛素信号通过激活mTOR信号通路启动下游分子调节细胞代谢,导致母体血管内皮损伤、子宫螺旋小动脉重构受损,以及炎症免疫反应异常等,参与PE的发生。通过探讨mTOR信号通路与PE发病的相关性,为PE的病理生理学研究及疾病的治疗提供理论基础。     

调节性T细胞和Notch1信号通路在原因不明复发性自然流产中的作用

目的探讨调节性T细胞(Treg)和Notch1信号通路在原因不明复发性自然流产(URSA)中的作用。方法流式细胞仪检测URSA患者(URSA组)及正常妊娠妇女(对照组)蜕膜CD4~+CD25~+T细胞Treg表达比例,real time RT-PCR及Western blotting检测蜕膜中CD4~+T细胞中Notch1信号通路和叉头转录因子家族3(Foxp3)表达情况。结果 URSA组CD4~+CD25~+T细胞/淋巴细胞、CD4~+Foxp3~+T细胞/淋巴细胞和CD4~+Foxp3~+T细胞/CD4~+T细胞比例均低于对照组(P0.05)。URSA组CD4~+T细胞中Notch1-Ic、RBPJκ、Foxp3 m RNA及蛋白表达均低于对照组。结论 URSA患者蜕膜CD4~+T细胞中Notch1信号通路和Foxp3表达下调,CD4~+CD25~+T细胞表达比例下降,提示URSA患者Notch1信号通路和Foxp3表达下调可能阻碍CD4~+T细胞转化为CD4~+CD25~+T细胞,进而诱发免疫排斥,诱导流产。     

Maternal Cerebral Blood Flow and Glucose Metabolism in Pregnancies Complicated by Severe Preeclampsia

Objective. To investigate maternal cerebral blood flow and glucose metabolism in pregnancies complicated by severe preeclampsia compared to normal pregnancies. Methods. A prospective study was conducted including six women with severe preeclampsia and nine normotensive women. Transcranial Doppler (TCD) was performed pre- and postoperatively. The anterior, middle, and posterior cerebral arteries (ACA, MCA, PCA) were selected for study; the cerebral perfusion pressure (CPP) and cerebral flow index (CFI) were calculated for each vessel. To evaluate the cerebral glucose metabolism, F-18 fluorodeoxyglucose positron emission tomography was performed postoperatively. Results. The preoperative CFI in each artery was similar in the comparisons between the two groups. However, the CPP in the MCA and the PCA was higher in the patients with severe preeclampsia. Compared to the preoperative values, the postoperative CPP and CFI in the ACA and the MCA were significantly increased in the severe preeclampsia group, while they were significantly decreased in the control group. Overall, the regional cerebral glucose uptake was not significantly different in comparisons between the two groups. In addition, there was no correlation between the cerebral Doppler indices and their corresponding regional cerebral glucose uptake. Conclusions. Severe preeclampsia was associated with an increase in the cerebral blood flow and perfusion pressure, particularly during the postpartum period, but it was not associated with a significant change in the cerebral glucose metabolism.     

子痫前期患者血清细胞因子表达谱及其临床意义

目的:研究子痫前期患者血清中细胞因子表达谱的变化及其临床意义。方法:①以Luminex液相芯片技术检测子痫前期患者(A组)16例、正常妊娠妇女(B组)19例、正常非孕妇(C组)12例3组人群血清IL-1β、IL-6、IL-8、IL-10、IFN-γ、TNF-α、MCP-1、VEGF、NT-proBNP等细胞因子表达水平,并进行比较;②收集、整理和分析3组对象血压、白细胞计数、尿蛋白及尿酸等临床常规检查指标,并与细胞因子表达谱的变化间进行对比分析。结果:①与B比,A组血清中IL-8、MCP-1、IL-6、TNF-α和VEGF5种细胞因子表达水平升高,有统计学差异(P<0.05),与疾病严重程度无明显相关性;②与B比,轻度(A1组)和重度(A2组)子痫前期者白细胞计数、尿酸水平均升高,有统计学差异(P<0.05或0.01);A1组与A2组间比较,尿酸水平有统计学差异(P<0.05),而白细胞计数水平则无统计学差异(P>0.05)。结论:子痫前期患者血清细胞因子表达呈炎症及血管损伤特征,尿酸水平可作为其疾病严重程度的监控指标。     

Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia

Objectives. Placental growth hormone (PGH) is a pregnancy-specific protein produced by syncytiotrophoblast and extravillous cytotrophoblast. No other cells have been reported to synthesize PGH Maternal. PGH Serum concentration increases with advancing gestational age, while quickly decreasing after delivery of the placenta. The biological properties of PGH include somatogenic, lactogenic, and lipolytic functions. The purpose of this study was to determine whether the maternal serum concentrations of PGH change in women with preeclampsia (PE), women with PE who deliver a small for gestational age neonate (PE + SGA), and those with SGA alone.

Study design. This cross-sectional study included maternal serum from normal pregnant women (n = 61), patients with severe PE (n = 48), PE + SGA (n = 30), and SGA alone (n = 41). Fetal cord blood from uncomplicated pregnancies (n = 16) and PE (n = 16) was also analyzed. PGH concentrations were measured by ELISA. Non-parametric statistics were used for analysis.

Results. (1) Women with severe PE had a median serum concentration of PGH higher than normal pregnant women (PE: median 23,076 pg/mL (3473–94 256) vs. normal pregnancy: median 12 157 pg/mL (2617–34 016); p < 0.05), pregnant women who delivered an SGA neonate (SGA: median 10 206 pg/mL (1816–34 705); p < 0.05), as well as pregnant patients with PE and SGA (PE + SGA: median 11 027 pg/mL (1232–61 702); p < 0.05). (2) No significant differences were observed in the median maternal serum concentration of PGH among pregnant women with PE and SGA, SGA alone, and normal pregnancy (p > 0.05). (3) Compared to those of the control group, the median umbilical serum concentration of PGH was significantly higher in newborns of preeclamptic women (PE: median 356.1 pg/mL (72.6–20 946), normal pregnancy: median 128.5 pg/mL (21.6–255.9); p < 0.01). (4) PGH was detected in all samples of cord blood.

Conclusions. (1) PE is associated with higher median concentrations of PGH in both the maternal and fetal circulation compared to normal pregnancy. (2) Patients with PE + SGA had lower maternal serum concentrations of PGH than preeclamptic patients without SGA. (3) Contrary to previous findings, PGH was detectable in the fetal circulation. The observations reported herein are novel and suggest that PGH may play a role in the mechanisms of disease in preeclampsia and fetal growth restriction.     

Effect of Magnesium Sulfate on the Osmotic Fragility and Lipid Peroxidation of Intact Red Blood Cells from Pregnant Women with Severe Preeclampsia

Objective: To evaluate the osmotic fragility and level of lipid peroxidation of red blood cells from pregnant women with severe preeclampsia, treated or not with MgSO₄. Methods: Osmotic fragility and lipid peroxidation of red blood cells was evaluated in 11 normotensive pregnant women and eleven pregnant women with severe preeclampsia. Results: MgSO₄ therapy, either in vivo or in vitro, leads to a reduction of the osmotic fragility and the level of lipid peroxidation of red blood cells from pregnant women with severe preeclampsia. Conclusions: Interaction of MgSO₄ with free radicals, by avoiding an excessive lipid peroxidation of the red blood cell membrane, would protect the membrane structure, avoiding in this way the increase in osmotic fragility.     

子痫前期患者外周血及胎盘组织中半乳糖凝集素1的表达及意义

目的：探讨子痫前期患者外周血及胎盘组织中半乳糖凝集素1（galectin-1,Gal-1）的表达及意义。方法：选取我院收治的早发型重度子痫前期患者53例为观察组,同期入院体检正常的孕妇53例为对照组。采用酶联免疫法检测血清Gal-1的浓度,经免疫组织化学法检测胎盘组织Gal-1蛋白的表达。结果：观察组和对照组外周血Gal-1浓度分别为（38.59±9.02）ng/L和（27.33±8.31）ng/L,2组比较差异有统计学意义（t=6.684,P＜0.001）。观察组胎盘组织Gal-1的表达高于对照组,差异有统计学意义（Z=5.632,P＜0.001）。结论：Gal-1可能与早发型重度子痫前期的发病有关,或可成为有价值的预测子痫前期的生物标记物。     

卵巢源雌性生殖干细胞增殖分化及其通路的研究进展

雌性生殖干细胞的发现打破了传统的"固定卵泡理论"。研究表明,在人和小鼠卵巢中,该类细胞定位于卵巢表面上皮,并可在其中检测到Oct4、Sox-2、Nanog、Vasa等生殖细胞和干细胞特异性标志物的存在;且2条重要的信号途径——Notch和Hippo在雌性生殖干细胞增殖与分化的过程中发挥重要的作用。