Angiopietin-2 在胎儿生长受限患者胎盘组织中的表达及意义

目的检测胎儿生长受限（FGR）患者胎盘组织中血管生成素-2（angiopoietin-2，Ang-2）的表达水平，并探讨其与FGR的关系。方法采用免疫组织化学方法（SP法）和逆转录聚合酶链反应（RT—PCR）检测FGR组和对照组的胎盘组织中Ang-2表达的定位和表达量的差异。结果1．S—P：（1）Ang-2在胎盘的绒毛滋养细胞、血管内皮细胞及血管周围细胞均有表达。（2）FGR组Ang-2的平均光密度较正常对照组显著下降（P〈0．05）。2．RT—PCR：FGR组Ang-2mRNA的表达量下降。于正常对照组相比有明显意义（P〈0．05）。结论妊娠晚期Ang-2水平显著下降可能是FGR发病机制中的一个重要因素。     

基质细胞衍生因子-1表达与胎儿生长受限相关性的研究

目的 探讨胎盘及外周血中基质细胞衍生因子-1(SDF-1)表达与胎儿生长受限（FGR）的相关性。方法 选取2020年6月至2021年6在广西壮族自治区妇幼保健院产科收治的50例FGR孕妇作为实验组,随机选50例同期新生儿出生体重正常的孕妇作为正常组,收集孕妇分娩前外周血及两组孕妇产后胎盘组织。首先通过H-E染色观察两组胎盘组织内部的病理学差异,ELISA实验检测两组孕妇血清中SDF-1的表达水平;然后采用IHC法检测两组胎盘组织中SDF-1蛋白的表达情况;最后结合qPCR技术检测两组胎盘组织中SDF-1 mRNA的表达。结果 H-E染色病理结果显示FGR孕妇胎盘组织内部细胞溶解,血管水肿破裂,绒毛间质纤维化及纤维蛋白样坏死,滋养层细胞肿胀,排列混乱。ELISA结果显示与对照组相比,FGR孕妇外周血中SDF-1表达降低（P<0.05）。IHC结果显示相较于对照组,实验组组胎盘组织SDF-1相对表达强度和阳性表达率明显减少。qPCR实验结果显示实验组中SDF-1 mRNA的表达水平（0.74±0.16）显著低于对照组,差异有统计学意义（P<0.05）。结论 通过检测孕妇SDF-...     

松驰素受体LGR7在人妊娠绒毛及胎盘组织中表达的研究

目的探讨松驰素受体LGR7在妊娠过程中的作用。方法应用免疫组织化学（免疫组化）链霉素抗生物素一过氧化物酶法和RT—PCR技术，对56例妊娠绒毛和胎盘组织中的LGR7检测。结果在早期妊娠的绒毛中，LGR7免疫反应呈现强阳性。主要分布于绒毛滋养层细胞的细胞膜上，在细胞滋养层细胞、合体滋养层细胞及滋养层细胞柱中都有较强的信号，并可见细胞滋养细胞的阳性反应明显强于合体滋养细胞；中、晚期妊娠的胎盘组织中LGR7呈现为强阳性或阳性，主要定位于合体滋养细胞的细胞膜上及毛细血管内皮细胞。免疫组化结果中，早期妊娠绒毛LGR7的强阳性率为90％，明显高于中晚期胎盘中的76．5％和73．7％，中、晚期妊娠分别与早期妊娠比较，差异均有统计学意义（P〈0．01）；但中期妊娠及晚期妊娠相比较，差异无统计学意义（P〉0．05）；早期妊娠的绒毛中LGR7mRNA的表达量为0．967±0．019，明显高于中晚期妊娠胎盘中的0．522±0．071和0．482±0．094，中、晚期妊娠分别与早期妊娠比较，差异均有统计学意义（P〈0．01）；中期妊娠及晚期妊娠比较，差异无统计学意义（P〉0．05）。结论LGR7可能是与妊娠早期滋养细胞侵袭有关的重要的因子，在妊娠的中晚期参与妊娠的维持。     

PPAR—γ和COX-2用于预测重度子痫前期合并胎儿生长受限的研究

目的研究过氧化物酶体增殖物激活型受体-1（peroxisomeproliferatoractivatedreceptor-γ,PPAR-1）和环氧化酶-2（Cyclooxγgenase-2,COX-2）在重度子痫前期及重度子痫前期合并胎儿生长受限（FGR）发病中的作用,以探讨重度子痫前期合并FGR的发病机制,为其早期诊断、早期治疗及病情预测提供新的理论和实验依据。方法收集重度子痫前期合并FGR患者30例（SPF组）,单纯重度子痫前期患者30例（sP组）,随机选取同期住院的正常晚期妊娠孕妇30例（NP组）,采用酶联免疫吸附法（ELISA）方法检测这三组孕妇母血血浆和脐血血浆中COX-2的表达。采用免疫组化技术检测胎盘组织中PPAR—γ蛋白的表达。结果SPF组、sP组、NP组脐血血清COX-2水平分别为（55．30±8．10）,（39．25±7．90）,（10．60±5．50）mg／mL,三组差异显著（P〈0．05）;SPF组、SP组、NP组孕妇血清COX-2水平分别为（35．25±6．58）,（26．13±6．10）,（7．20±5．36）mg／mL,三组亦有显著差异（P〈0．05）;SPF组孕妇血清与脐血血清中COX-2水平呈正相关（r=0．526,P〈0．01）;SPF组、sP组、NP组胎盘组织中PPAR-1的阳性表达率分别为87．5％、53．1％、29．6％,三组差异显著（P〈0．05）。结论1．COX-2的升高在重度子痫前期和重度子痫前期合并FGR的预测中起着重要作用,COX-2明显升高可预测在重度子痫前期的发病基础上出现FGR;2．出现重度子痫前期合并FGR的胎盘组织PPAR-1蛋白呈强阳性表达;3．通过测定孕母血清COX-2水平能预测胎儿血清COX-2水平。     

AS、VEGF在胎儿生长受限患者脐血及胎盘部位的表达及意义

目的通过检测脐血与胎盘部位血管生长抑素（angiostatin,AS）、血管内皮生长因子（vascular endotrelial growtr factor,VEGF）的表达,探讨其与胎儿生长受限（fetal growth restriction,FGR）发病的关系。方法取80例产妇（正常妊娠组50例,FGR组30例）分娩后采脐血和胎盘绒毛组织,检测AS、VEGF在脐血中的水平及其在胎盘部位的表达。结果①脐血中：在FGR组AS平均水平显著高于对照组（P〈0.05）;VEGF平均水平显著低于对照组（P〈0.05）。②胎盘中：在FGR组绒毛滋养细胞AS的表达强度较正常对照组显著增强（P〈0.05）,而VEGF的表达降低,差异有统计学意义（P〈0.05）。结论血管生长抑素（AS）与血管内皮生长因子（VEGF）浓度的变化可能在胎儿生长受限（FGR）的发病中起重要作用。     

Ki67在正常妊娠和胎儿生长受限患者胎盘组织中的表达和意义

目的 通过检测增殖蛋白Ki67在正常妊娠各期和FGR患者胎盘组织中的表达，探讨其在正常妊娠中的作用及与FGR的关系。方法 采取免疫组化法取正常妊娠各期和FGR患者胎盘组织共42例，检测Ki67蛋白的表达。结果 （1）Ki67主要在细胞滋养细胞中表达强，在合体滋养细胞中呈阴性。（2）Ki67在早、中、晚期胎盘组织阳性表达率无统计意义（P〉0．05），表达强度早、中期及中、晚期无显著差别（P〉0．05）；早、晚期有显著差异（P〈0．05）：FGR组与正常妊娠晚期组胎盘中Ki67表达阳性率、表达强度之间无显著差异（P〉0．05）。结论 （1）Ki67在妊娠早期、中期表达强度高，说明滋养细胞处于高增殖状态。（2）Ki67随妊娠进展表达下调，提示与胎盘老化和分娩发动有关。（3）FGR组Ki67表达阳性率上调说明细胞滋养细胞的增生。     

生长分化因子15在子痫前期胎盘滋养细胞中的表达及意义

目的探讨生长分化因子-15（GDF-15）在子痫前期患者胎盘滋养细胞中的表达,探讨其在子痫前期发病机制中的作用。方法选择2009年12月至2010年10月在青岛市市立医院住院分娩的子痫前期孕妇140例,其中早发型轻度子痫前期孕妇35例（早发轻度组）,晚发型轻度子痫前期孕妇35例（晚发轻度组）,早发型重度子痫前期孕妇35例（早发重度组）,晚发型重度子痫前期孕妇35例（晚发重度组）;另选同期健康孕妇35例为对照组。采用RT—PCR检测胎盘滋养细胞中GDF-15mRNA的表达量;采用免疫组化方法检测胎盘滋养细胞中GDF-15蛋白的表达。结果RT—PCR显示子痫前期各组胎盘滋养细胞中GDF-15mRNA表达水平均高于对照组,差异有统计学意义（P〈0．05）;但子痫前期各组间分别比较,差异无统计学意义（P〉0．05）。免疫组化显示GDF-15表达于胎盘滋养细胞的细胞浆和细胞外基质中,并在各组胎盘滋养细胞中均表达。子痫前期各组胎盘滋养细胞中GDF-15蛋白表达水平均高于对照组组,差异有统计学意义（P〈0．05）;但子痫前期各组间分别比较,差异无统计学意义（P〉0．05）。结论GDF-15在子痫前期胎盘滋养细胞中表达升高,GDF-15的表达水平变化可能与子痫前期发病有关。     

HGF在胎儿生长受限胎盘中的表达及其意义

目的检测胎儿生长受限(FGR)的胎盘组织肝细胞生长因子(HGF)的表达,探讨其与FGR的关系。方法应用免疫组织化学SP法检测15例晚期正常妊娠胎盘和15例FGR胎盘HGF的表达。结果FGR组胎盘中HGF染色强度明显高于正常妊娠组(P<0.01)。结论FGR胎盘HGF的高表达可能是子宫胎盘血流减少导致绒毛滋养细胞增殖的结果。     

轴突导向因子-1在胎儿生长受限胎盘组织中的表达及意义

目的：探讨神经轴突导向因子?1（ netrin?1）在胎儿生长受限患者胎盘组织中的表达变化。方法分析33例胎儿生长受限患者（其中18例为胎儿生长受限合并妊娠期高血压患者）及24例正常妊娠孕妇相关数据,并利用Real time?polymerase chain reaction （ RT?PCR）和Western印迹检测netrin?1在胎盘组织中的表达差异。结果①临床数据显示胎儿生长受限患者与正常孕妇在年龄、孕周、体重指数、血压、胎盘重量和出生体重等方面存在显著差异（ P＜0．05或P＜0．01）;②免疫组化结果显示netrin?1在胎盘中存在表达。③ RT?PCR及蛋白质印迹法显示胎儿生长受限患者胎盘组织中netrin?1的表达明显降低。结论 ne?trin?1表达降低可能是导致宫内胎儿生长受限的机制之一。     

Syncytin在子痫前期胎盘组织中表达水平的检测及其临床意义

目的探讨子痫前期（preeclampsiaic,PE）胎盘组织中syncytin的表达情况。方法选择确诊PE孕妇19例及孕周相匹配的正常妊娠孕妇21例,入组病人共40例。获取胎盘组织后,RT—PCR法检测syncytin mRNA转录水平,比较两组检测结果。结果PE组和正常妊娠组病例胎盘组织均检测到syncytin mRNA,与正常对照组（5．81±1．96）比较,PE病例胎盘组织syncytin mRNA水平明显降低（1．34±0．89,P〈0．01）。结论胎盘syncytin表达下调与PE发病密切相关。     

Hypoxia-inducible factor-2alpha is involved in enhanced apoptosis in the placenta from pregnancies with fetal growth restriction

The aim of the present study is to investigate whether hypoxia-inducible factors (HIF-1alpha, HIF-2alpha, HIF-1beta) are involved in enhanced apoptosis in the human placenta from pregnancies with fetal growth restriction (FGR). Placental samples were obtained from women with normal term pregnancy (n = 18) or from pregnancy with FGR (n = 12). Placenta apoptosis was assessed by the terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) staining. The expressions of HIF-1alpha, HIF-2alpha, and HIF-1beta were examined by immunohistochemical analysis. Enhanced apoptosis was observed in the placenta from pregnancies with FGR compared with normal term placenta. The apoptosis index in FGR group (1.45 +/- 1.26%) was significantly higher than that in the normal control group (0.18 +/- 0.16%; P < 0.01). There were no significant differences in the intensity of the staining for HIF-1alpha and HIF-1beta expressions between two groups, while HIF-2alpha was overexpressed in the placenta from pregnancies with FGR group (P < 0.05). The upregulation of HIF-2alpha protein expression in the placenta from pregnancies with FGR may, at least in part, be involved in the increased placental apoptosis.     

Expression of vascular endothelial growth factor receptors 1, 2 and 3 in placentas from normal and complicated pregnancies

Extensive angiogenesis and invasion of the maternal decidua by trophoblasts are essential for the development and function of the placenta. Vascular endothelial growth factors (VEGF), placenta growth factor (PlGF) and their receptors VEGFR-1/Flt-1, VEGFR-2/KDR and VEGFR-3/Flt4 have important roles in vasculogenesis and angiogenesis. We have studied the localization of these proteins by immunohistochemistry and Western blotting in the placenta and of PlGF in maternal serum, and their association with diabetes, pre-eclampsia, fetal growth restriction (FGR) and fetal alcohol syndrome (FAS). VEGFR-1 and VEGFR-3 were detected mainly in the syncytiotrophoblastic layer whereas VEGFR-2 was detected in the vascular endothelial cells of the placenta. VEGFR-1, but not the other receptors, showed increased expression in placental syncytiotrophoblasts from 50% of patients with severe pre-eclampsia and FGR when compared with normal placentas. PlGF was undetectable in 38 of 44 samples of amniotic fluid of mothers with normal and complicated pregnancies. However, maternal serum PlGF concentrations were significantly lower in pre-eclamptic patients and in those with FGR when compared to diabetic women or healthy controls. These results suggest that low maternal serum PlGF and increased placental expression of its receptor VEGFR-1 are associated with pre-eclampsia and FGR.     

Human trophoblast invasion and spiral artery transformation: the role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction

During early human pregnancy extravillous cytotrophoblasts invade the uterus and spiral arteries transforming them into large vessels of low resistance. Failure of trophoblast invasion and spiral artery transformation occurs in preeclampsia and fetal growth restriction (FGR); these processes are not well understood. Recent studies have suggested that cytotrophoblasts that invade spiral arteries mimic the endothelial cells they replace and express PECAM-1. It was also reported that in preeclampsia, cytotrophoblasts fail to express PECAM-1 and that failure to express endothelial cell adhesion molecules may account for failed trophoblast invasion. Despite the possible importance of adhesion molecules in trophoblast invasion, no study has systematically investigated the expression of PECAM-1 in the placental bed throughout the period of invasion, particularly in the myometrial segments where the key failure occurs. There are no studies on PECAM-1 expression in the placental bed in FGR. We have examined the expression of PECAM-1 in placental bed biopsies and placentas from 8 to 19 weeks of gestation and in the placenta and placental bed in the third trimester in cases of preeclampsia, FGR, and control pregnancies. PECAM-1 was expressed on endothelium of vessels in the placenta and placental bed but not by villous or extravillous trophoblasts in normal or pathological samples. These findings do not support a role for PECAM-1 in normal invasion or in the pathophysiology of preeclampsia or FGR.     

Transforming Growth Factor-β Expression in Human Placenta and Placental Bed in Third Trimester Normal Pregnancy, Preeclampsia, and Fetal Growth Restriction

Normal human pregnancy depends on physiological transformation of spiral arteries by invasive trophoblasts. Preeclampsia (PE) and fetal growth restriction (FGR) are associated with impaired trophoblast invasion and spiral artery transformation. Recent studies have suggested that transforming growth factor (TGF)-beta3 is overexpressed in the placenta of PE patients and that this may be responsible for failed trophoblast invasion. There are, however, no studies on TGF-betas in the placenta in FGR or in the placental bed in PE or FGR. In this study we have used immunohistochemistry, Western blot analysis, and enzyme-linked immunosorbent assay to examine the expression of TGF-beta1, TGF-beta2, and TGF-beta3 in placenta and placental bed of pregnancies complicated by PE and FGR and matched control pregnancies. The results show that TGF-beta1, -beta2, and -beta3 are not expressed in villous trophoblasts but are present within the placenta. TGF-beta1, -beta2, and, to a much lesser extent, TGF-beta3 were present within the placental bed but only TGF-beta2 was present in extravillous trophoblast. No changes in expression of either isoform were found in placenta or placental bed in PE or FGR compared with normal pregnancy. These data are not consistent with overexpression of TGF-beta3 being responsible for failed trophoblast invasion in PE. Our findings suggest that the TGF-betas do not have a pathophysiological role in either PE or FGR.     

Placental leptin in normal, diabetic and fetal growth-retarded pregnancies

Leptin expression in third trimester placenta (p) and leptin concentrations in umbilical cord blood (cb) were investigated in normal pregnancies [n = 10 (p), 31 (cb)] and abnormal pregnancies complicated with (i) maternal insulin-dependent diabetes [IDDM: n = 3 (p), 13 (cb)], (ii) gestational diabetes [GD: n = 2 (p), 10 (cb)] and (iii) fetal growth retardation [FGR: n = 5 (p), 5 (cb)]. By in-situ hybridization and immunohistochemistry, placental leptin mRNA and protein were co-localized to the syncytiotrophoblast and villous vascular endothelial cells. Leptin receptor was immunolocalized to the syncytiotrophoblast. Relative to controls, the FGR group was characterized by low concentrations of placental and cord blood leptin. In a twin pregnancy, the normal-sized infant exhibited more placental and cord blood leptin than its growth-retarded twin. In contrast, both diabetic groups exhibited high concentrations of placental leptin mRNA and protein. The IDDM group exhibited the highest concentrations of leptin in cord blood. No change was observed in the expression of the leptin receptor in either the growth-retarded or diabetic pregnancies. In conclusion, the localization of placental leptin suggests that it may be released into both maternal and fetal blood. Furthermore, in fetal growth-retarded and diabetic pregnancies, the changes in leptin expression in the placenta and in leptin concentrations in umbilical cord blood appear to be related.     

尾加压素Ⅱ与GPR14 mRNA在子痫前期患者胎盘组织中的表达及意义

目的研究子痫前期患者胎盘组织尾加压素Ⅱ（UⅡ）及G蛋白偶联受体14（GPR14）mRNA的表达变化及其与子痫前期发病的关系。方法采用RT-PCR方法对25例子痫前期（子痫前期组,其中轻度15例,重度10例））患者和20例正常足月孕妇（正常妊娠组）和胎盘组织中UⅡ和GPR14 mRNA表达水平进行检测。结果胎盘组织UⅡmRNA表达水平在轻度子痫前期组,重度子痫前期组均明显高于正常妊娠组,差异有统计学意义（P均〈0.05）。重度子痫前期组孕妇胎盘GPR14mRNA表达水平明显高于对照组,差异有统计学意义（P〈0.05）。结论子痫前期患者胎盘UⅡ及其受体基因表达升高,可能在子痫前期胎盘缺血缺氧动脉粥样硬化的发生中发挥重要作用。     

可溶性Flt-1在子痫前期患者胎盘组织中的变化及意义

目的研究可溶性血管内皮生长因子受体1(soluble fms-like tyrosine kinase receptor 1, sFlt-1)mRNA在子痫前期患者胎盘组织中的表达与定位,探讨其与子痫前期的关系.方法通过半定量RT-PCR及原位杂交方法分别检测子痫前期患者和健康孕妇胎盘组织中sFlt-1 mRNA的表达及定位.结果正常胎盘组织和子痫前期胎盘组织中均存在sFlt-1 mRNA,子痫前期胎盘组织中sFlt-1 mRNA表达明显高于正常胎盘组织(P<0.01).sFlt-1 mRNA主要分布在胎盘绒毛滋养细胞及血管内皮细胞胞浆内.结论胎盘组织中sFlt-1的高表达可能参与了子痫前期的病理生理过程.     

基质金属蛋白酶-9预测胎儿宫内生长受限的意义

目的探讨基质金属蛋白酶-9(MMP-9)与胎儿宫内生长受限(FGR)的关系及其预测FGR的意义。方法回顾性分析了自2006年9月至2008年10月在上海市第六人民医院分娩的部分孕妇,其中FGR组29例,正常组41例。于孕28周时抽取母体静脉血,分离血清后放置冰箱待用,于足月分娩时同时抽取母静脉血及脐静脉血,分离血清,用ELISA法测定血清中MMP-9浓度。结果FGR组脐血及母血MMP-9的浓度均低于正常组(分别为1.76±0.22*,1.50±0.20△+);而且,孕28周时母血的MMP-9高于足月分娩时母血中的MMP-9;脐血中MMP-9浓度明显高于母血中的浓度(P0.01),脐血与母血中MMP-9浓度无相关性(P0.05)。结论MMP-9与FGR有关,早期检测基质金属蛋白酶(MMP-9)有助于预测FGR;母体静脉血不能完全替代脐静脉血中MMP-9浓度的检测。