妊娠高血压综合征合并胎儿生长受限胎盘组织血管细胞粘附分子1的表达

目的：探讨血管细胞粘附分子1（vascular cell adhesion molecule-1,VCAM-1)在妊娠高血压综合征（简称妊高征）合并胎儿生长受限（fetal growth restriction,FGR)发病过程中的作用。方法：采用免疫组化法测定30例妊高征合并FGR患者、28例非妊高征合并FGR及30例正常妊娠者胎盘组织中血管内皮及滋养细胞的VCAM－1表达。结果：妊高征合并FGR组胎盘底蜕膜内血管内皮VCAM－1的表达阳性率（80％）及表达强度（＋＋＋）14例，与正常妊娠组25％（＋＋＋）0例及非妊高征合并FGR组155％（＋＋＋）0例相比明显增高（P＜0．005），而前两者间无显著差异，随妊高征病情加重，其表达强度逐渐增强；胎盘绒毛毛细血管VCAM－1阳性表达强度妊高征合并FGR组（73．3％）和非妊高征FGR组（67．8％）明显增强，与正常组（10％）相比差异有显性（P＜0．005）；所有GFR患者胎盘滋养细胞VCAM－1表达强度明显降低（妊高征FGR为0％，非妊高征FGR组3．6％，正常组40％），并且在妊高征组随妊高征病情加重其表达强度急剧减低。结论：胎盘血管内皮及绒毛滋养细胞异常表达的VCAM－1参与了妊高征引起FGR的病理生理过程，可以作为判定妊高征对胎盘损伤程度的一个指标。     

妊娠高血压综合征患者胎盘组织中血管内皮生长因子的表达

目的　探讨血管内皮生长因子（VEGF）在妊娠高血压综合征（妊高征）患者胎盘组织中的表达及对妊高征患者胎盘滋养细胞功能和绒毛毛细血管网形成的影响。方法　采用免疫组织化学SP法检测21例正常孕妇（对照组）,60例妊高征患者（妊高征组,其中轻、中、重度妊高征患者各20例）胎盘组织VEGF的表达强度。结果　VEGF主要表达于胎盘绒毛滋养细胞;中度及重度妊高征患者胎盘绒毛滋养细胞VEGF表达强度均明显低于对照组及轻度妊高征患者(P＜0.05),而轻度妊高征患者与对照组比较,差异无显著性(P＞0.05),各组间蜕膜组织VEGF表达强度差异无显著性(P＞0.05)。　结论　VEGF在胎盘中主要由绒毛滋养细胞分泌,妊高征患者VEGF分泌减少,可能是引起局部胎盘绒毛及血管病变的原因之一。     

妊娠高血压综合征患者胎盘组织中肝细胞生长因子及其受体的表达

目的探讨肝细胞生长因子(hepatocyte growth factor，HGF)及其受体(c-met)在正常妊娠妇女及妊高征患者胎盘组织中的表达及对妊高征胎盘滋养细胞功能的影响。方法不同程度妊高征晚孕和正常妊娠晚孕孕妇共78例，采用免疫组织化学SP法检测胎盘组织HGF及c-met的表达强度。结果HGF主要表达于绒毛间质细胞胞浆。重度妊高征组胎盘绒毛间质细胞HGF表达强度显著低于正常晚孕组(H=7．395，P=0．007)，而轻度及中度妊高征组与正常晚孕组比较，差异无显著性(H=0．869，P=0．351；H=0．017。P=0．817)。c-met主要表达于滋养细胞。重度妊高征患者胎盘绒毛滋养细胞c-met表达强度显著低于正常晚孕组(H=4．577，P=0．032)，而轻度及中度妊高征组与正常晚孕组比较，差异无显著性(H=0．178，P=0．673；H=0．824，P=0．364)。HGF与c-met表达强度呈负相关(phi关联系数：7．809，P=0．005)。结论HGF在胎盘中主要由绒毛间质细胞分泌，其受体c-met表达于滋养细胞表面，妊高征患者HGF分泌减少可能是引起其胎盘出现生理性血管重铸障碍继而发病的原因。     

妊娠高血压综合征患者胎盘血管内皮生长因子的表达及其意义

目的　探讨胎盘血管内皮生长因子 (VEGF)在妊娠高血压综合征 (妊高征 )患者中的表达及其与胎盘血管网络构建、胎盘重量及新生儿体重的关系。方法　采用蛋白免疫印迹技术测定 2 5例正常妊娠妇女 (正常妊娠组 )及 2 5例妊高征患者 (妊高征组 )的胎盘组织中VEGF的表达。采用免疫组织化学法 ,用抗F8因子抗体标记两组孕妇胎盘中的血管密度。两组孕妇分娩后 ,测量新生儿身长、体重 ,并胎盘称重。结果　 (1)妊高征组和正常妊娠组孕妇胎盘VEGF积分吸光度值分别为2 4793± 6 5 79、4190 3± 110 0 9;胎盘血管密度分别为 (6 1± 11)和 (78± 11)个 / 40 0×视野。两组比较 ,差异均有极显著性 (P <0 0 1) ,且与妊高征患者病情严重程度相关。 (2 )妊高征组胎盘重量 [(4 6 0±5 9)g]较正常妊娠组 [(5 73± 99)g]显著下降 (P <0 0 1)。 (3)妊高征组新生儿体重为 (3176± 5 0 3)g,较正常妊娠组的 (34 6 8± 493)g显著下降 (P <0 0 5 ) ;而新生儿身长在两组间比较 ,差异无显著性(P >0 0 5 )。(4 )正常妊娠组中 ,胎盘VEGF的表达与血管密度、胎盘重量和新生儿体重的相关系数分别为 0 82 3、0 6 71、0 888;妊高征组分别为 0 90 5、0 85 9、0 732 ,两者均呈显著正相关 (P <0 0 1)。而VEGF表达与新生儿身长不相关     

胎儿宫内生长迟缓患者的胎盘免疫病理学观察

目的：观察胎儿宫内生长迟缓（IUGR）患者的胎盘免疫病理学改变,并探讨IUGR的发病机理。方法：采用免疫组织化学技术,对22例不明原因IUGR（不明原因IUGR组）、10例妊娠高血压综合征（妊高征）合并IUGR（妊高征合并IUGR组）、23例正常产妇（正常妊娠组）的胎盘免疫病理学改变进行观察。结果：⑴3组胎盘绒毛内血管IgG的阳性例数分别为：不明原因IUGR组19例,妊高征合并IUGR组10例,正常妊娠组17例,3组比较,差异无显著性（P＞0.05)。⑵不明原因IUGR组与妊高征合并IUGR组的绒毛内血管IgG阳性例数分别为8例及4例,而正常妊娠组则无一例阳性。⑶不明原因IUGR组与妊高征合并IUGR组的胎盘蜕膜血管IgG、IgM阳性例数,以及滋养细胞IgM染色强度均高于正常妊娠组。而不明原因IUGR组与妊高征合并IUGR组之间比较,差异显著性（P＞0.05)。⑷不明原因IUGR组中,抗心磷脂抗体（ACA）阳性与阴性患者的胎盘免疫复合物沉积状况比较,差异无显著性（P＞0.05)。结论：胎盘免疫复合物沉积在IUGR的发病中起重要作用。不明原因IUGR与妊高征合并IUGR具有相似的胎盘免疫病理改变。ACA导致IUGR的机理是否与胎盘免疫复合物的沉积有关,尚需进一步证实。     

胎盘生长因子与妊娠高血压综合征发病的相关性研究

目的　探讨胎盘生长因子(PLGF)与妊娠高血压综合征（妊高征）发病的关系。方法用酶联免疫吸附法(ELISA)、免疫组织化学染色法和逆转录-聚合酶链反应法(RT-PCR)检测23例妊高征患者(妊高征组)、20例正常妊娠妇女(正常妊娠组)的外周血及其新生儿脐静脉血PLGF水平、胎盘蜕膜PLGF蛋白及其mRNA表达。结果　(1)妊高征组外周血PLGF水平［(112.7±63.8)μg/L］低于正常妊娠组［(200.3±140.9)μg/L］,两组比较,差异有显著性(P<0.05),且与新生儿体重和胎盘重量呈正相关,相关系数分别为0.4、0.6。(2)妊高征组合体滋养细胞、绒毛间质和蜕膜PLGF表达均显著低于正常妊娠组(P<0.01,P<0.01,P<0.05),其合体滋养细胞PLGF表达水平与妊高征病情的轻、重有关。(3)妊高征组胎盘和蜕膜组织总PLGFmRNA表达均显著低于正常妊娠组(P<0.05,P<0.05),尤其胎盘组织主要表现为PLGF-2mRNA表达明显下降(P<0.01)。结论　PLGF的表达异常在妊高征发病中起着重要作用。     

血管内皮生长因子与妊娠高血压综合征发病的相关性研究

目的探讨血管内皮生长因子（VEGF）与妊娠高血压综合征（妊高征）发病的相关性。方法采用酶联免疫吸附法检测23例妊高征患者（妊高征组）外周血及其新生儿脐静脉血VEGF水平,定量免疫组化及定量逆转录聚合酶链反应检测患者胎盘和蜕膜组织中VEGF表达情况,并以20例健康孕妇(正常妊娠组)为对照。结果（1）妊高征组外周血VEGF水平为［(10.4±3.8)ng/L,±s,下同］,明显低于正常妊娠组的(17.0±9.3)ng/L。（2）胎盘合体滋养细胞及蜕膜间质滋养细胞均有VEGF强阳性染色。经计算机扫描图像处理,正常妊娠组绒毛合体滋养细胞VEGF表达为(75.0±9.0)平均灰度,间质细胞为(60.5±6.4)平均灰度,均显著高于妊高征组的(69.0±8.9)平均灰度和(55.0±7.3)平均灰度。正常妊娠组VEGF表达为(45.4±4.0)平均灰度,显著高于妊高征组的(42.5±3.8)平均灰度。（3）胎盘、蜕膜组织均有3种不同片断长度的VEGFmRNA扩增,正常妊娠组胎盘组织VEGF总峰度比为2.8±1.0,较妊高征组(4.6±3.2)极明显降低（P<0.01）。正常妊娠组蜕膜组织VEGF总峰度比为3.9±1.5,也较妊高征组(6.3±2.9)极明显降低,（P<0.01）。结论妊高征患者VEGF表达障碍发生在蛋白质翻译和表达水平;VEGF的异常表达在妊高征胎盘缺氧中具有重要的作用。     

妊高征患者胎盘滋养细胞中转化生长因子β1的表达及意义

目的 :探讨胎盘组织中转化生长因子 β1 (TGF β1 )的定位 ,检测滋养细胞中TGF β1mRNA的表达水平 ,评估TGF β1在妊娠高血压综合征 (妊高征 )中的作用。方法 :用免疫组化法对 30例正常孕妇、2 5例妊高征孕妇的胎盘组织进行TGF β1定位 ;用逆转录 聚合酶链反应 (RT PCR)检测正常妊娠滋养细胞 6例、妊高征滋养细胞 6例中TGF β1mRNA表达水平 ,并进行定量分析。结果 :(1 )胎盘TGF β1主要位于绒毛小叶的合体滋养细胞及细胞滋养细胞 ;(2 )与正常组比较 ,妊高征组胎盘TGF β1的平均光密度显著增加(P <0 .0 5) ;(3)与正常滋养细胞比较 ,妊高征滋养细胞TGF β1mRNA的表达强度显著增强(P <0 .0 5)。结论 :胎盘组织中TGF β1主要位于胎盘小叶的合体滋养细胞、细胞滋养细胞 ,胎盘滋养细胞合成TGF β1的增多与妊高征的发生有关     

妊娠高血压综合征胎盘滋养细胞中胰岛素样生长因子Ⅱ及其mRNA的表达

目的　检测胎盘滋养细胞中胰岛素样生长因子Ⅱ (insulin likegrowthfactorⅡ ,IGF Ⅱ )及其mRNA的表达 ,评估IGF Ⅱ在妊娠高血压综合征 (妊高征 )发病中的作用。　方法　 (1)用免疫组化法检测正常及妊高征孕妇胎盘组织中IGF Ⅱ的表达 ,并用计算机图像分析系统进行定量分析比较。 (2 )用逆转录 聚合酶链反应 (RT PCR)检测正常妊娠及妊高征胎盘滋养细胞IGF ⅡmRNA表达水平 ,并通过紫外凝胶图像分析进行定量分析比较。　结果　 (1)IGF Ⅱ主要位于绒毛小叶的合体滋养细胞及细胞滋养细胞。此外 ,也存在于羊膜绒毛层 ,但染色较以上两种细胞明显减弱。(2 )与正常妊娠胎盘组 (0 36 0± 0 0 72 )比较 ,妊高征组IGF Ⅱ的平均光密度 (0 32 4± 0 0 4 2 )显著降低 (P <0 .0 5 )。 (3)妊高征胎盘滋养细胞IGF ⅡmRNA的表达 (0 72± 0 72 )亦显著低于正常妊娠者(0 96± 0 30 ,P <0 .0 5 )。　结论　胎盘滋养细胞表达IGF Ⅱ减少可能与妊高征的发病有关。     

重度妊高征胎盘的形态计量学观察

为探讨妊高征胎盘形态计量学特点，应用图像分析系统对２９例重度妊高征（妊高征组）和２９例正常妊娠（对照组）的胎盘床血管的胎盘绒毛进行形态计量学检测。结果：妊高征组胎盘绒毛具有合体细胞结节、细胞滋养细胞增生、绒毛基底膜增厚、纤维素样坏死和血管合体细胞膜的绒毛与对照组相比差异显著（Ｐ〈０．０５）。妊高征组胎盘绒毛直径、周长和面积参数均显著低于对照组（Ｐ〈０．０５）。妊高征组胎盘床螺旋动脉妊娠生理性改变缺     

Tissue kallikrein and kininogen levels in fetoplacental tissues from normotensive pregnant women and women with pregnancy-induced hypertension

OBJECTIVES: An imbalance of vasoconstrictor and vasodilator substances in the placenta has been postulated in the pathogenesis of pregnancy-induced hypertension (PIH). There is however little information available on the kallikrein-kinin system (KKS) in women with PIH. The aim of this study therefore was to determine tissue kallikrein and kininogen levels and their distribution patterns in fetoplacental tissues from both normotensive pregnant (NTP) women and women with PIH. STUDY DESIGN: The study group consisted of 24 women, 12 of whom had normal pregnancies, while 12 had PIH. Portions of amnion, chorion laeve, placental plate chorion, fetal placenta and maternal placenta were dissected from each freshly delivered placenta. Tissue kallikrein (total, active and inactive) and kininogen levels were estimated using a synthetic chromogenic substrate, S-2266 and an enzyme immunoassay, respectively. The data were analysed using Mann-Whitney U and Kruskal-Wallis tests. RESULTS: No significant differences were found for total, active and inactive tissue kallikrein levels in all fetoplacental tissues between both groups. However, kininogen levels were found to be significantly lower in chorion laeve, placental plate chorion, fetal placenta and maternal placenta from women with PIH when compared to those in similar tissues from NTP women. CONCLUSION: These findings suggest the presence of an abnormality in the kallikrein-kinin system in the placentas of women with PIH, which requires further study.     

Corticotropin-releasing hormone in maternal and cord plasma in pre-eclampsia.

The concentration of corticotropin-releasing hormone (CRH) in maternal plasma increases greatly during the last trimester of normal pregnancy. This CRH has been proposed to originate from the placenta. We studied plasma immunoreactive CRH in 46 uncomplicated pregnancies, in 10 pregnant women with chronic hypertension, in 17 women with pregnancy-induced hypertension (PIH) and in 24 women with pre-eclampsia, and correlated it to the levels of corticotropin (ACTH) and cortisol. CRH levels were greatly increased in women with pre-eclampsia, less significantly in women with PIH, while no change was found in pregnant women with chronic hypertension. ACTH levels also were increased in pregnancies with pre-eclampsia or PIH and there was a positive correlation between CRH and ACTH levels. CRH levels in cord venous plasma were significantly increased in pregnancies with pre-eclampsia but cortisol did not show any significant increase. These findings suggest that placental release of CRH into the maternal and fetal circulation is increased in pre-eclampsia.     

Study on the expression of angiotensin II (ANG II) receptor subtype 1 (AT1R) in the placenta of pregnancy-induced hypertension

OBJECTIVE: To study the expression of angiotensin II (ANG II) receptor subtype 1 (AT(1)R) in the human placenta with pregnancy-induced hypertension (PIH). METHODS: Immunohistochemistry was used to detect the expression of AT(1)R in placental tissues of 30 patients with PIH and 10 patients with normal pregnancies (control group). The PIH tissues were further divided into 3 groups: mild PIH group, moderate PIH group and severe PIH group. Each group consisted of 10 patients. A high-resolution pathological image analysis system (HPIAS-1000) was used to determine the quantity of AT(1)R expression. RESULTS: The integral optical density and area of staining in the syncytiotrophoblast (STB) layer and villous endothelium of the placenta were significantly increased in PIH patients, in the moderate and severe PIH groups, as compared with the control group (P < 0.05), indicating that the expression of AT(1)R was highly increased in PIH. However, there was no significant difference between normal pregnancy and the mild PIH group (P > 0.05). Furthermore, statistically significant differences in AT(1)R expression were observed between mild, moderate and severe PIH groups (P < 0.05). CONCLUSION: The expression of AT(1)R is statistically significantly increased in the STB layer and villous endothelium of human placenta with PIH. Expression increases with the severity of the disease. Increased expression may be involved in the pathogenesis of PIH.     

妊高征患者胎盘组织中胎盘异铁蛋白的表达及其与血清VCAM-1的相关性研究

目的 :观察胎盘异铁蛋白 (PLF)在妊娠高血压综合征 (妊高征 )患者胎盘组织中的表达 ,及其与患者血清中血管细胞粘附分子 1(VCAM 1)的相关性。方法 :用免疫组化染色法检测 4 5例妊高征胎盘组织 (妊高征组 )和 15例正常妊娠胎盘组织 (正常组 )中PLF的表达 ,通过高清晰度彩色病理图文分析系统对其定量分析 ;用酶联免疫吸附双抗体夹心法 (ELISA)测定血清VCAM 1含量。结果 :在中、重度妊高征胎盘组织中PLF的表达明显低于轻度妊高征组和正常组 (P <0 .0 1) ;妊高征组血清VCAM 1水平 (1310± 177ng/ml)比正常组 (6 0 9± 72ng/ml)升高显著 (P <0 .0 1) ;胎盘组织中PLF表达水平与血清VCAM 1水平呈负相关 (r=- 0 .5 8,P <0 .0 1)。结论 :妊高征患者胎盘组织中PLF表达水平降低 ,与血清VCAM 1水平呈负相关 ,这可能与妊高征的发病有关     

Umbilical-placental blood flow gradient during the early second trimester of pregnancy.

OBJECTIVE: To characterize umbilical-placental blood flow gradient during early second trimester of pregnancy. METHODS: Forty normal pregnant women with a singleton fetus gave their informed consent to participate in this study. All scans were preformed between 12 and 20 weeks' gestation using the simultaneous multigate spectral Doppler imaging (MS-SDI) modality available on the Diasonics Synergy system. The umbilical-placental circulation was scanned at three locations: (1) umbilical artery at the cord insertion, (2) superficial placenta at a point close to the cord insertion, and (3) deep placenta branches at the area adhere to the decidua basalis. The mean value of pulsatility index (PI) and resistance index (RI) were recorded. RESULTS: PI and RI were both significantly lower in the superficial and deep placenta compared with the cord insertion area. No significant differences were found comparing between superficial and deep placenta. In 30 women we found lower values and in 10 women we found a higher value of PI and RI in the superficial and deep placenta compared with the cord insertion. Four of five cases with complicated pregnancies occurred in patients with negative placental gradient compared with only one case with positive placental gradient (p < 0.05). CONCLUSIONS: In this preliminary report the umbilical placental blood flow gradient was characterized during the early second trimester of normal pregnancy. The presence of decreasing gradient was established. Absent or opposite gradient between the umbilical artery and the placental vessels was associated with adverse pregnancy outcome.     

妊高征患者胎盘中一氧化氮合酶-mRNA转录强度的变化及意义

目的探讨妊高征患者胎盘中内皮型一氧化氮合酶（ｅＮＯＳ）含量减少的原因。方法采用定量的逆转录－聚合酶链反应（ＲＴＰＣＲ）技术,检测９例正常足月妊娠妇女胎盘和１２例妊高征患者胎盘中ｅＮＯＳｍＲＮＡ转录强度的变化。结果（１）正常足月妊娠妇女胎盘和妊高征患者胎盘中均存在ｅＮＯＳｍＲＮＡ。（２）妊高征患者胎盘中ｅＮＯＳｍＲＮＡ的转录强度显著低于正常足月妊娠妇女（Ｐ＜０．０５）。结论妊高征患者胎盘中ｅＮＯＳ含量的减少是由于ｅＮＯＳｍＲＮＡ转录强度下降所致。     

妊娠肝内胆汁淤积症胎盘超微结构及其表皮生长因子受体表达的研究

目的　观察妊娠肝内胆汁淤积症 (intrahepaticcholestasisofpregnancy ,ICP)胎盘超微结构病理改变和表皮生长因子受体 (EGFR)的表达 ,研究胆汁酸对滋养细胞的毒性作用及其对胎儿生长发育的影响。　方法　透射电镜观察 2 2例ICP患者胎盘组织 ,其中ICP合并胎儿生长受限 (fetalgrowthrestriction ,FGR) 7例、ICP未合并FGR 15例 ,应用免疫组化方法和逆转录 聚合酶链反应 (RT PCR)技术测定胎盘滋养细胞表皮生长因子受体 (EGFR)的表达 ,并和 15例正常晚期胎盘比较。　结果　电镜显示 ,ICP胎盘合体滋养细胞较对照组微绒毛减少、内质网扩张、线粒体肿胀或髓鞘样改变 ,核染色质异常分布。ICP合并FGR组上述病理改变更为明显 ,绒毛间质毛细血管减少 ,并出现大量胶原原纤维。ICP合并FGR组胎盘EGFR免疫组化的平均A值 (0 .2 39± 0 .0 17)和ICP未合并FGR组EGFR免疫组化的平均A值 (0 .2 5 3± 0 .0 15 )均比对照组 (0 .384± 0 .0 16 )低 ,差异具非常显著性 (P<0 .0 1)。ICP合并FGR组胎盘EGFRmRNA指数 (0 .2 30± 0 .0 4 8)和ICP未合并FGR组EGFRmRNA指数 (0 .2 31± 0 .0 4 2 )表达均比对照组 (0 .4 6 0± 0 .0 5 1)低 ,差异具非常显著性 (P <0 .0 1) ,ICP合并FGR组与ICP未合并FGR组之间胎盘EGFR的表达无显著性差异 (P     

彩色多普勒监测妊高征孕妇子宫胎盘血流变化

应用彩色多普勒血流显像技术监测了３１例妊高征孕妇及７４例正常孕妇子宫胎盘血流，同时测定血中雌三醇、胎盘泌乳素、血栓素代谢产物、前列环素代谢产物及ＴＸＢ２／６ＫＰ比值。结果表明：正常孕妇子宫动脉及胎儿脐动脉的时间平均血流速度及血流量明显高于妊高征孕妇。     

Relation of placental prolactogen and E3 in the blood of pregnant women to placental grading by ultrasonography and its clinical significance

Serum HPL and E3 of normal pregnant women and some pathologic pregnancies were dynamically measured and the relationship between their levels and placental gradings were investigated. The peak values of HPL and E3 were found in 13.16 +/- 7.49 and 15.68 +/- 6.51 days before delivery. The serum concentrations of the two hormones in women with severe PIH syndrome, postdate pregnancy and intrauterine fetal growth retardation (IUGR) were lowered. E3 declined earlier than HPL Analysis of the HPL, E3 levels in comparison with placental grading showed that the decline of the two hormones was mainly found in patients with grade III placenta.