细胞基质蛋白Cyr61和CTGF在子痫前期发病中的作用

目的:检测细胞基质蛋白Cyr61和CTGF在重度子痫前期患者胎盘组织中的定位及表达,研究它们在子痫前期发病中的作用。方法:采用免疫组化SP法和实时荧光定量聚合酶链式反应(quantitative real time polymerase chain reaction,real-time PCR)方法检测胎盘组织中Cyr61和CTGF的表达,其中重度子痫前期患者34例,正常妊娠16例。结果:(1)细胞基质蛋白Cyr61和CTGF在正常妊娠孕妇及重度子痫前期患者胎盘组织中均有表达;(2)Cyr61在重度子痫前期患者胎盘组织的表达水平低于正常妊娠孕妇胎盘(P<0.01);(3)CTGF在重度子痫前期患者胎盘组织的表达水平高于正常妊娠孕妇胎盘(P<0.05);(4)Cyr61和CTGF mRNA在重度子痫前期患者胎盘组织的表达水平呈负相关(P<0.01)。结论:Cyr61表达下调和CTGF过度表达与子痫前期的发病有关,并在该病的发病过程中起到一定的作用。     

Adipocytokine expression in placentas from pre-eclamptic and chronic hypertensive patients.

OBJECTIVE: Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients. METHODS: Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction. RESULTS: Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis. CONCLUSIONS: This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.     

富半胱氨酸61与妇科肿瘤

富半胱氨酸61(Cyr61)是结缔组织生长因子(CCN)家族中具有代表性的成员,其富含半胱氨酸残基的分泌性肝索连接蛋白具有多模组结构.具有诱导血管生成,促进细胞黏附、转移及诱导多药耐药形成等效用,在子宫内膜癌、宫颈癌、卵巢癌、子宫肌瘤及子宫内膜异位症的发生发展中起重要作用.     

富半胱氨酸61与妇科肿瘤

富半胱氨酸61（Cyr61）是结缔组织生长因子（CCN）家族中具有代表性的成员,其富含半胱氨酸残基的分泌性肝素连接蛋白具有多模组结构。具有诱导血管生成,促进细胞黏附、转移及诱导多药耐药形成等效用,在子宫内膜癌、宫颈癌、卵巢癌、子宫肌瘤及子宫内膜异位症的发生发展中起重要作用。     

Differential expression of nestin in normal and pre-eclamptic human placentas

BACKGROUND: Nestin is a type VI intermediate filament protein originally described in neural stem cells. Recent reports have documented nestin expression in endothelium of newly formed blood vessels and suggested its role as a marker of capacity for neovascularization and angiogenesis in endothelial cells. The aim of this study was to investigate the differential expression of nestin in normal and pre-eclamptic human placentas. METHODS: Placental tissues from 12 women with severe pre-eclampsia and 15 gestational age-matched normotensive women were collected at the time of their cesarean section. Western blot analysis for each placental tissue was performed for nestin quantification. Immunohistochemical staining was employed to localize nestin-positive cells and to investigate differential staining intensity in each placental cell. RESULTS: Nestin expression was detected in all of the normal and pre-eclamptic placental tissues by Western blotting. Compared with the normal placentas, tissues from severe pre-eclamptic placentas showed higher expression of nestin (p<0.001). Nestin immunoreactivity was localized only to endothelial cells of chorionic villi. However, mesenchymal connective tissue cells, cytotrophoblasts, syncytiotrophoblasts, and decidual cells did not reveal any specific signal for nestin. CONCLUSIONS: We suggest that the capacity for neovascularization and angiogenesis in endothelial cell is increased in pre-eclamptic placenta compared to that from normal pregnancy. Such changes may be a compensatory mechanism for the reduced maternofetal exchanges and long-lasting fetal hypoxia in pre-eclamptic pregnancy. Furthermore, these changes in endothelial cells of chorionic villi in pre-eclamptic pregnancy may give an explanation for fetal response to pre-eclamptic conditions.     

Three-dimensional assessment of the morphology of the umbilical artery in normal and pre-eclamptic placentas

AIM: Pre-eclampsia is one of the main causes of intrauterine growth retardation. Although there are many studies performed in this setting showing the course of the umbilical vessels within the umbilical cord along with its structural changes, studies are lacking with regard to intraplacental vasculature and its structural changes. METHODS: We investigated whether the vascular pattern differed in preeclamptic placentas in terms of intraplacental course and morphometry of the umbilical artery by using vascular corrosion cast technique. Furthermore, cross-sections taken from umbilical artery branches at different levels within the placenta, were examined with both light and scanning electron microscopy (SEM). RESULTS: Vascular corrosion casts generated in both pregnancy groups should be defined with the main umbilical artery divided into 2-4 primary branches. No significant difference was seen between normal and pre-eclamptic groups regarding the diameters of primary and secondary branches and the number of cotyledons contained (P > 0.05). However, microscopic studies demonstrated expanded intervillous spaces in the placentas of pre-eclamptic pregnancies. Under SEM, distortion on the endothelial surface of the umbilical artery and an increase in vessel diameter and wall thickness have been determined in pre-eclamptic placentas. Furthermore, the branching pattern and changes affecting the endothelial surface of the umbilical artery have been shown three-dimensionally in pre-eclamptic placentas, using corrosion cast technique and SEM, respectively. CONCLUSION: While microscopic findings were consistent with the Doppler ultrasonography findings, namely higher systole/diastole ratio and increased resistance (RI) and pulsatile (PI) index in the umbilical artery, no clear morphometric change has been observed.     

In vitro effect of bioactive natriuretic peptides on perfusion pressure in placentas from normal and pre-eclamptic pregnancies

The number of placental vascular guanylate-coupled receptors, corresponding to bioactive natriuretic peptide receptors is greater in preeclampsia, but there are no clear data about atrial natriuretic peptide (ANP) concentration in preeclampsia. The influence of various doses of ANP and urodilatin (URO) on placental perfusion pressure in preeclampsia was investigated by perfusing 16 human placentas in vitro. The placental vessels were submaximally preconstricted by continuous infusion of N-ω-nitro-l-arginine (NOLA). Perfusion pressure was measured continuously. Over 180 min various doses of αANP or URO were administrated (25, 50, 100, 200 nmol/l, 2 min increments). The effects of pretreatment with the guanylate cyclase inhibitor, LY 83583 was also examined. We found that ANP and URO attenuated NOLA-induced vasoconstriction, that URO given in higher doses produced stronger vasocilation than ANP, and that the mean decrease of perfusion pressure was higher in preeclampsia. The possibility of a non cGMP-mediated pathway of ANP and URO action should be considered. Received: 11 August 1998 / Accepted: 15 January 1999     

Trophoblast deportation in pre-eclamptic pregnancy.

OBJECTIVES--To examine the deportation of trophoblast cells into the maternal blood in pre-eclamptic (gestational proteinuric hypertension) and normal pregnancy. DESIGN--The monoclonal anti-cytokeratin antibody JMB2 was used in the APAAP technique to label trophoblast cells in cell smears of uterine vein blood obtained at caesarean section. SUBJECTS--10 women with proteinuric pre-eclampsia requiring caesarean section, 10 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia and five control women who had never been pregnant. RESULTS--Three populations of trophoblast cells were identified; two mononuclear cytotrophoblast types with diameters varying from 11-14 microns and 19-25 microns respectively, and multinucleated syncytiotrophoblast cells varying in size from 23-88 microns. Women with pre-eclampsia had more trophoblast cells in uterine vein blood than were found in pregnant women without pre-eclampsia. There was no correlation between the numbers of trophoblast cells and the stage of gestation or severity of the pre-eclampsia, although an acute maternal or fetal event necessitating delivery was associated with increased deportation of trophoblast. Mononuclear cytotrophoblast cells were detected in the peripheral blood of only 1 of 5 pre-eclamptic patients, despite their presence in the uterine vein blood of all 5 women. CONCLUSIONS--Trophoblast deportation is increased in pre-eclamptic pregnancy, with both cytotrophoblast and syncytiotrophoblast present in the uterine vein blood, but there is no correlation with the severity of the disease. In some cases cytotrophoblast may also enter the peripheral circulation.     

Plasma acid phosphatase in normal and pre-eclamptic pregnancy

Plasma acid phosphatase activity was measured in nonpregnant, normal pregnant, and severely pre-eclamptic women. The third trimester of pregnancy was associated with a rise in plasma acid phosphatase and severe pre-eclampsia with a marked rise in this enzyme. Possible sources of this elevation in acid phosphatase activity are the placenta, kidneys, pregnancy-associated plasma proteins, and blood platelets—with platelets the most likely.     

Confocal laser scanning microscope study of terminal villi vessels in normal term and pre-eclamptic placentas

The aim of this study was to compare immunocytochemical confocal scanning laser microscopy measures of villus capillarization in control placentas with pre-eclamptic ones. Accordingly, placentas from normal term pregnancies (n=3) and cases of late-onset pre-eclampsia without intrauterine growth retardation (IUGR) featuring normal uterine artery Doppler (n=3) were analyzed by confocal scanning laser microscopy (CSLM), which is a powerful technique for obtaining three-dimensional reconstructions of any kind of blood vessels (arteries, veins, capillaries). A laser light beam is used in order to detect CD34 antibody-related immunofluorescence, which is a marker of endothelial cells. Villus capillarization was assessed by estimating the following parameters: number of pixels, mean, maximum and minimum immunofluorescence amplitude. Our results show a significant hyper-ramification of the capillary loop in pre-eclamptic placentas, featuring irregular profile and narrow lumina. Such findings support the hypothesis that several agents causing angiogenesis and vasoconstriction affect villus vessels in pre-eclamptic placentas, thus promoting a lasting condition of fetal hypoxia by decreasing endothelial surface and materno-fetal exchanges.     

Stereologic examination of placentas from mothers who smoke during pregnancy

OBJECTIVE: Structural changes in the placenta might contribute to the lower birth weight seen among infants born to mothers who smoke cigarettes. In this study, a morphologic examination and a stereologic quantitation of placentas from mothers who smoked cigarettes and who did not smoke cigarettes during pregnancy were performed. STUDY DESIGN: Twenty-five placentas from mothers who did not smoke cigarettes, 15 placentas from mothers who smoked 5 to 10 cigarettes per day, 16 placentas from mothers who smoked 11 to 20 cigarettes per day, and 16 placentas from mothers who smoked >20 cigarettes per day were delivered at term after normal pregnancies and were fixed by dual perfusion. The volume and the surface area of villi, the trophoblast volume, and the volume and the surface area and length of villous capillaries were estimated. A measurement of the concentration of cadmium in serum was used to assess the validity of information concerning smoking habits. RESULTS: No differences were shown in the total volume of placenta between the groups. The estimated volume and surface area and the calculated lengths for villous capillaries were significantly reduced in all 3 groups of smokers. A significant increase of the trophoblast volume was observed in the mothers who smoked cigarettes. CONCLUSION: Cigarette smoking during pregnancy influences the placental vasculature. The reduced dimensions of fetal capillaries in villi may affect the placental blood flow, and the diminished area for exchange of gases and nutrients between the mother and the fetus will increase the risk of fetal undernourishment.     

重度子(癎)前期和正常妊娠胎盘中微小RNA-155及富含半胱氨酸蛋白61的差异表达

目的 探讨微小RNA-155(microRNA-155,miR-155)和富含半胱氨酸蛋白61(cysteine-rich 61,CYR61)在重度子(癎)前期和正常妊娠胎盘中差异表达的意义. 方法取18例重度子(癎)前期患者(孕36～40周)胎盘和同期分娩且孕周匹配的18例正常产妇胎盘,从mRNA水平检测miR-155和CYR61 mRNA的表达情况,并在蛋白水平检测CYR61的表达情况. 结果 与正常产妇胎盘相比,重度子(癎)前期组胎盘的miR-155表达水平明显增高(165.7±16.4和527.9±49.1,t=7.00,P＜0.01);而CYR61 mRNA表达水平及蛋白表达水平均降低(31.7±2.7和16.4±1.2,t=5.10,P＜0.01;36.4±1.5和19.7±1.2,t=36.26,P＜0.01).重度子(癎)前期和正常妊娠胎盘组织中的miR-155与CYR61 mRNA的检测结果的相关性分析显示,两组内两者表达均呈负相关(r=-0.52,P＜0.05;r=-0.57,P＜0.05). 结论重度子(癎)前期患者胎盘中miR-155的上调,可能与促血管生成因子-CYR61的表达下降有关.miR-155、CYR61可能共同参与了子(癎)前期胎盘血管缺陷的发生.     

Immunohistochemical study of transferrin receptor expression in the placenta of pre-eclamptic pregnancy

Transport of iron from the mother to the fetus is essential for the normal development of the fetus and abnormalities in the transferrin receptor (TFR) on the placental trophoblasts might have some crucial effects on the fetal iron metabolism. The present study was undertaken to determine whether there are any changes in the expression of the transferrin receptor in the placenta from pre-eclamptic mothers. An immunohistochemical study using antibodies specific for C-terminus and N-terminus regions of the TFR revealed that TFR expression by syncytiotrophoblasts around chorionic villi is markedly reduced in placentae from pre-eclamptic pregnancies compared to those from normal pregnancies and pregnancies at early gestational age that terminated by abortion. The same result, although to a lesser extent, was obtained even in trophoblasts which were located around atrophic villi with fibrotic changes in the interstitium, or which invaded into the deciduas. The expression of human chorionic gonadotropin (HCG) on those cells was observed to the same extent in the normal and pre-eclamptic pregnancy groups. The concentration of TFR in the peripheral blood also decreased in pre-eclampsia. These results suggest that TFR synthesis in the pre-eclampsia, especially in the placental trophoblasts, is decreased.     

人类白细胞相关抗原-G及其各亚型mRNA在正常妊娠及重度子痫前期患者胎盘组织中的表达

目的 研究人类白细胞相关抗原-G（HLA-G）及其各个亚型mRNA在正常妊娠及重度子痫前期患者胎盘组织中的表达.方法 选取2005-01-2005-06第四军医大学唐都医院10例重度子痫前期患者（研究组）及10例正常妊娠胎盘组织（对照组）,应用荧光定量RT-PCR比较两组间HLA-G及其各个亚型mRNA（HLA-G1、G2、G3、G4、G5、G6）的表达.结果 与对照组相比,重度子痫前期患者胎盘组织中总HLA-G mRNA显著降低,以HLA-G1、HLA-G3降低为主,差异有统计学意义（P＜0.05）.结论 HLA-G1与HLA-G3 在胎盘组织中的低表达可能与妊娠期高血压疾病的发病和病理生理过程有关.     

Endothelial function in normal and pre-eclamptic pregnancy: a hypothesis.

Pre-eclampsia is the most common medical complication of pregnancy. Immunologic maladaptation has been suggested to play a role in the etiology of pre-eclampsia. The putative misalliance of fetal trophoblast with maternal tissue in the uteroplacental vascular bed may give rise to an increase in oxygen free radicals. Oxygen free radicals and lipid peroxides might form the link between the hypothetical immunologic maladaptation and the endothelial cell damage known to occur in pre-eclampsia. Recent studies have demonstrated the existence of increased oxygen free radical production in pre-eclampsia. Oxygen free radicals and lipid peroxides decrease vascular prostacyclin and EDRF release and increase thromboxane A2 and endothelin release. The hypothesis is put forward that in pre-eclampsia a proposed immunologic maladaptation causes an increase in oxygen free radicals by decidual lymphoid cells. A decrease in vasodilatory autocoids, prostacyclin and EDRF may result from the endothelial cell damage induced by oxygen free radicals. Uteroplacental prostacyclin production might be essential as escape mechanism. The adequacy as escape mechanism seems to determine the final clinical outcome.     

人类白细胞相关抗原-G及其各亚型mRNA在正常妊娠及重度子(癎)前期患者胎盘组织中的表达

目的 研究人类白细胞相关抗原-G(HLA-G)及其各个亚型mRNA在正常妊娠及重度子(癎)前期患者胎盘组织中的表达.方法 选取2005-01-2005-06第四军医大学唐都医院10例重度子(癎)前期患者(研究组)及10例正常妊娠胎盘组织(对照组),应用荧光定量RT-PCR比较两组间HLA-G及其各个亚型mRNA(HLA-G1、G2、G3、G4、G5、G6)的表达.结果 与对照组相比,重度子(癎)前期患者胎盘组织中总HLA-G mRNA显著降低,以HLA-G1、HLA-G3降低为主,差异有统计学意义(P＜0.05).结论 HLA-G1与HLA-G3 在胎盘组织中的低表达可能与妊娠期高血压疾病的发病和病理生理过程有关.