子(癎)前期和子(癎)的治疗进展

子癎前期和子癎是妊娠期特有的严重并发症,是导致孕产妇和围生儿病率和死亡率升高的主要原因。临床除了对症治疗外,及时发现和掌握疾病发展的进程,并予妥善处理,对保证母亲安全及降低胎儿和新生儿并发症意义重大。现就近几年的治疗进展作一综述。     

子(癎)前期及子(癎)围生儿预后分析

目的:了解子(癎)前期及子(癎)对围生儿的影响,探讨终止妊娠时机及方式.方法:对2003年1月至2005年12月收住我院产科的子(癎)前期及子(癎)患者的临床资料进行回顾性分析.结果:子(癎)前期及子痫患者的围生儿发病率及死亡率随孕妇病情加重而升高;随孕周增加,其发病率及死亡率逐渐降低,其中36周围生儿发病率及死亡率最低,剖宫产比阴道分娩围生儿发病率及死亡率低.结论:围生儿发病率及死亡率与子(癎)前期及子痫的发病时间及严重程度密切相关,适时终止妊娠可提高围生儿存活率,剖宫产可降低围生儿发病率及死亡率.     

子(癎)前期胎盘组织syncytin及其受体ASCT2的表达

目的研究syncytin及其受体ASCT2在子前期(PE)胎盘组织中的表达。方法胎盘组织来源于广东省人民医院和广州医学院附属第三医院2006年7月至2007年7月住院分娩病例。依孕周匹配,入组孕妇共48例,分为轻度PE组(17例),重度PE组(13例)和正常对照组(18例),应用实时PCR方法检测syncytin及ASCT2mRNA的转录水平,比较检测结果。结果各组均检测到syncytin及ASCT2mRNA。与正常对照组(6.37±2.74)相比,轻、重度PE组胎盘组织syncytinmRNA水平明显降低(1.69±1.34,1.38±1.29),差异有统计学意义(P<0.01);对照组及轻、重度PE组ASCT2mRNA水平(分别为5.51±3.05,3.51±2.93,2.97±1.48)差异无统计学意义(P>0.05);轻、重度PE两组间syncytin及ASCT2mRNA差异均无统计学意义(P>0.05)。结论胎盘syn-cytin表达下调可能与PE发病有关,但其转录水平与病变程度似不相关,其受体ASCT2与PE发生无明显相关性。     

子(癎)前期胎盘组织差异表达基因PP2ACβ的初步研究

目的 寻找并克隆子(癎)前期胎盘组织高表达基因蛋白磷酸酶2A催化亚基β(PP2ACβ),研究其mRNA及蛋白水平的表达,探讨其在子(癎)前期中的作用.方法 标本取自2004年5月至2004年12月天津中心妇产科医院重度子(癎)前期及正常孕妇各30例.应用荧光mRNA差异显示技术(FDD)发现并克隆子(癎)前期胎盘组织差异表达的基因PP2ACβ,进一步应用半定量RT-PCR及免疫组化技术分析差异表达基因PP2ACβmRNA及其蛋白水平PP2A的表达.结果 通过FDD发现PP2ACβ基因在子(癎)前期胎盘组织中高表达,半定量RT-PCR证实PP2ACβ mRNA在子(癎)前期胎盘组织中的表达(0.888±0.104)高于正常胎盘组织(0.692±0.099),差异有统计学意义(P＜0.05),免疫组化验证其蛋白水平PP2A的表达(0.14±0.02)亦高于正常(0.12±0.02),差异有统计学意义(P＜0.05).结论 FDD可有效用于筛选子(癎)前期胎盘组织差异表达基因;PP2A可能通过促进胎盘滋养层细胞的凋亡及阻碍血管生成而参与子(癎)前期的发病.     

血管内皮生长因子受体2在子(癎)前期患者胎盘中的表达及其意义

目的 探讨子痢前期患者胎盘中血管内皮生长因子受体2(KDR)的表达与胎盘血管病变的关系,研究子(癎)前期的发病机制.方法 对中国医科大学附属第二医院2004年1至11月间收治的重度子(癎)前期患者22例、轻度子(癎)前期患者20例和同期正常妊娠妇女20例,采用免疫组化SP法检测其胎盘中KDR的表达情况,记数胎盘间质的平均微血管密度(MVD)值.结果 子(癎)前期重度患者胎盘中KDR的表达显著低于轻度患者和正常孕妇(P＜0.01),子(癎)前期轻度组较正常对照组KDR表达明显降低(P＜0.05).子(癎)前期重度组患者胎盘中MVD值明显低于轻度组和正常对照组(P＜0.01),子(癎)前期轻度组较正常对照组MVD值降低(P＜0.05).子(癎)前期患者和正常孕妇胎盘中KDR表达与MVD值的变化呈显著正相关(r=0.855,P＜0.01).结论 KDR表达水平降低可能参与引起胎盘血管发育不良.从而导致子(癎)前期的发生和发展.     

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.     

子(癎)前期孕妇中性粒细胞相关因子与胎儿的关系

目的:了解中性粒细胞在子前期胎儿中的状态,探讨其在胎儿患病中的作用。方法:采用流式细胞术检测20例子前期患者和20例正常妊娠孕妇肘静脉血和脐静脉血中中性粒细胞粘附分子CD11b的表达,同时采用酶联免疫吸附实验检测两组血浆IL-8和弹性蛋白酶的浓度。结果:①子前期组母体静脉血CD11b的平均对数荧光强度指数、血浆IL-8和弹性蛋白酶的浓度均高于正常妊娠组(P<0.05);②子前期组脐静脉血CD11b的平均对数荧光强度指数高于正常妊娠组(P<0.05),但血浆IL-8和弹性蛋白酶的浓度与正常妊娠组比较无统计学差异(P>0.05);③胎儿脐静脉血中的中性粒细胞CD11b平均对数荧光强度指数与母体静脉血中的中性粒细胞CD11b平均对数荧光强度指数有正相关关系(r=0.590,P<0.01)。结论:子前期胎儿中性粒细胞的激活与母体中性粒细胞的激活相关,胎儿循环中存在中性粒细胞的激活,推测中性粒细胞在子前期胎儿病率中有一定作用。     

妊娠期糖尿病合并子(癎)前期对母儿的影响

目的 研究妊娠期糖尿病(gestational diabetes mellitus,GDM)合并子(癎)前期对新生儿出生体重及母儿并发症的影响.方法 回顾分析中国医科大学附属盛京医院及解放军202医院2002-01-2004-12收治的GDM病例共127例,其中合并子(癎)前期者35例(Ⅱ组,余为Ⅰ组),以同期子(癎)前期35例(Ⅲ组)及正常妊娠35例(Ⅳ组)为对照,比较四组间新生儿出生体重之间的差异,以及Ⅰ、Ⅱ组母儿并发症.结果 (1)GDM孕妇子(癎)前期的发生率(27.6%,35/127) 明显高于同期子(癎)前期的发生率(6.97%,353/5066),差异有统计学意义(P＜0.01).(2)Ⅰ组与Ⅱ组新生儿出生体重差异无统计学意义(P＞0.05),Ⅱ组明显高于Ⅲ组及Ⅳ组(P均＜0.01).(3)所有GDM病例中小于胎龄儿2例,均合并重度子(癎)前期.(4)Ⅰ组与Ⅱ组孕妇羊水过多、酮症酸中毒等的发生率及新生儿红细胞增多症等的发生率差异无统计学意义(P均》0.05);Ⅱ组孕妇手术产的发生率高于Ⅰ组(P＜0.05),新生儿窒息及转科的发生率也明显高于Ⅰ组(P＜0.05).结论 GDM易合并子(癎)前期,且GDM合并子(癎)前期者中,孕妇早产、胎膜早破等围生期并发症增多,新生儿大于胎龄儿及低血糖等并发症亦增多.     

瘦素在子癎前期患者胎盘和血清的表达和意义

目的 探讨子癎前期患者胎盘和血清中瘦素的表达变化及其和子癎前期发病的关系.方法 采用免疫组化SP法检测45例子癎前期患者(研究组,其中重度组28例,轻度组17例)和30例同期正常妊娠妇女(对照组)胎盘瘦素水平,并用酶联免疫吸附实验检测两组孕妇产前血清瘦素水平.结果 (1)两组胎盘瘦素均在合体滋养细胞胞浆表达,随病情加重,染色逐渐加深,胎盘瘦素与子癎前期存在线性相关关系.(2)研究组、轻度组、重度组和对照组血清瘦素浓度分别为(10.41±4.78)ng/ml、(6.33±1.87)ng/ml、(12.88±4.27)ng/ml、(5.73±2.19)ng/ml,轻度组稍高于对照组但无统计学意义(P>0.05),研究组和对照组、轻和重度组、重度组和对照组相比,均有性统计学意义(P<0.01),瘦素表达水平和病情严重程度呈正相关.(3)血清瘦素与体重指数无相关性(P>0.05);但其与收缩压、舒张压及平均动脉压均呈正相关(r=0.602、0.566和0.585,P均<0.05).结论 瘦素在子癎前期患者胎盘和血清中均高表达,高瘦素水平参与子癎前期的发生和发展.     

硫氧还蛋白和硫氧还蛋白结合蛋白-2在子宫内膜异位症的表达及意义

目的:探讨血清和腹水中硫氧还蛋白(thioredoxin,TRX)及硫氧还蛋白结合蛋白-2(Trxbinding protein-2,TBP-2)的含量与子宫内膜异位症(endometriosis,EMs)的相关性。方法:应用病例-对照研究的方法,分别收集34例EMs患者(病例组)和32例非EMs妇女(对照组)的外周血清和腹水样本,通过酶联免疫吸附法(ELISA)测定血清及腹水中TRX、TBP-2的水平。结果:TRX在病例组血清、腹水中的表达量均高于对照组,差异有统计学意义(P0.05)。TBP-2在病例组血清、腹水中的表达量均明显低于对照组,差异有统计学意义(P0.05)。结论:EMs患者血清和腹水中TRX及TBP-2表达的变化可能与EMs的发生、发展有关。     

雌激素受体α在子痫前期胎盘的表达及临床意义

目的:通过比较雌激素受体α(ERα)在子痫前期胎盘和正常胎盘中组织细胞的定位,探讨ERα与子痫前期疾病的相关性及其临床意义。方法:用免疫组化SP法检测28例正常足月妊娠胎盘组织和33例子痫前期胎盘组织中ERα的表达。结果:免疫组织化学结果显示两组的ERα均呈阳性表达,子痫前期组的ERα在胎盘细胞滋养细胞的细胞质内或细胞核内的阳性表达率高于正常孕妇组(P<0.05)。结论:免疫组化检查定位于胎盘绒毛细胞滋养细胞、绒毛毛细血管管壁细胞和绒毛间质纤维组织成纤维细胞的ERα作为实现雌激素功能的介导中枢,可能通过调控雌激素的作用参与了子痫前期的发生和发展过程。     

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。     

Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia

Preeclampsia is a hypertensive disorder in pregnant women, which can be the leading cause of maternal and neonatal death or premature birth. Although the cause of preeclampsia is still not clear, local or systemic oxidative stress may explain the pathological features associated with this complication. However, it is not clear whether oxidative stress is the cause or the result of preeclampsia. For this purpose, the present meta-analysis was intended to evaluate the oxidant and antioxidant status in women with preeclampsia.Relevant studies were identified after a preliminary investigation of research articles published up to September 2017.In the overall analysis, including 2953 cases and 3621 controls, a statistically significant reduction in total antioxidant capacity, nitric oxide, superoxide dismutase, glutathione, vitamin E and C was observed in preeclampsia women. On the other hand, a statistically significant increase in malondialdehyde, protein carbonyl, total peroxide, glutathione peroxidase, catalase and uric acid were observed in preeclampsia women. The increased products of oxidative stress, which were found in the present meta-analysis might be an underlying mechanism for endothelial dysfunction in preeclampsia.This meta-analysis provides a scientific support that primary reduction of antioxidant capacity and increased levels of oxidative stress products may induce a condition in which the pathways responsible for blood pressure homeostasis are disrupted. In conclusion, it is hypothesized when oxidative stress is established, a protective response is induced by increasing some antioxidants. Further studies are warranted to investigate the role of dietary supplementation and genetic variation in women with different ethnicity.     

Expression levels of seven candidate genes in human peripheral blood mononuclear cells and their association with preeclampsia

Objective: To evaluate the peripheral blood mononuclear cell (PBMC) expression levels of hemeoxygenase 1 (HMOX-1), superoxide dismutase 1 (SOD-1), vascular endothelial growth factor A (VEGF-A), transforming growth factor beta 1 (TGF-β1), interleukin (IL)-6, IL-15 and AdipoQ genes to study their association with preeclampsia (PE). Methods: A total of 177 pregnant women were recruited: 108 cases and 69 controls. Quantification of gene expression was measured by quantitative real-time polymerase chain reaction (PCR) using TaqMan probes. Results: Underexpression of VEGF-A and TGF-β1 was a constant in most of the cases (80.91% and 76.36%, respectively) and their expression was associated with onset and/or severity of disease (p values?Conclusion: PBMC underexpression of VEGF-A and TGF-β1 is a hallmark of PE in the study population.     

Reduced uterine perfusion pressure model is not successful to mimic severe preeclampsia

The aim of the study was to investigate maternal (hemoglobin, hematocrit, and biochemical parameters of blood and urine) and fetal parameters (number and weight of alive fetus) of preeclampsia in a rat model. Placental oxidative stress markers (protein carbonyl, malondialdehyde) and placental antioxidant values (CuZn-superoxide dismutase, glutathione peroxidase) were also measured. Preeclampsia was induced experimentally in timed-pregnant Sprague-Dawley rats by using the reduced uterine perfusion pressure (RUPP) model. Placental oxidative stress that plays a key role in the pathophysiology of placenta-related disorders, most notably preeclampsia (PE) and intrauterine growth restriction (IUGR) were demonstrated by using RUPP model. On day 14 of gestation, silver clips were placed around the aorta below the renal arteries and on the left and right uterine arcade at the ovarian artery. In the RUPP model animals (n = 15), when compared with the normotensive controls (n = 15), arterial pressure on day 19 of gestation was significantly higher in the RUPP rats (151.7 ± 17.6 mmHg) than normal pregnant rats (113.9 ± 11.4 mmHg). The RUPP rats showed a significant increase in protein excretion when compared with the normal pregnant rats (0.3 ± 0.04 vs 0.47 ± 0.07 g/dL) (p < 0.05). Associated with the hypertension in RUPP rats, placental levels of malondialdehyde (2.4 ± 0.2 vs. 1.6 ± 0.2 umol/gm tissue) and protein carbonyl (1.4 ± 0.3 vs. 0.9 ± 0.3 nmol/mg protein) were increased, while superoxid dismutase (0.03 vs 0.42 U/mg protein) and glutathione peroxidase (1.04 ± 0.31 vs 0.76 ± 0.22 U/g protein) were decreased. Pup number (6.6 ± 3.1 vs. 9.93 ± 2.0) and litter weight (17.4 ± 7.7 vs. 22.9 ± 6.7 g) were lower in the preeclamptic group. None of the complete blood counts and biochemical values other than sodium and chlorine were significantly different in preeclamptic group. Our findings suggest that the RUPP model cannot mimic severe preeclampsia; however, further studies using different settings may be helpful to obtain a preeclampsia model that is capable of succesfully producing severe preeclampsia findings.     

Increased breath markers of oxidative stress in normal pregnancy and in preeclampsia

OBJECTIVES: The purpose of this study was to compare the intensity of oxidative stress in normal pregnancy, preeclampsia, and nonpregnant women using a breath test. STUDY DESIGN: We studied primiparous women in third trimester pregnancy (38 uncomplicated, 26 with preeclampsia) and 60 nonpregnant control subjects. Volatile organic compounds (VOCs) in alveolar breath were analyzed by gas chromatography/mass spectroscopy to construct the breath methylated alkane contour (BMAC), a 3-dimensional display of abundance of C4-C20 alkanes and monomethylated alkanes. RESULTS: The mean volume under curve (VUC) of the BMAC was significantly higher in preeclampsia patients than in normal pregnant women (P < .003) and nonpregnant control subjects (P < .005). A predictive model employing 5 VOCs distinguished preeclampsia from uncomplicated pregnancy (sensitivity = 92.3%, specificity = 89.7%; cross-validated sensitivity = 88.5%, specificity = 79.3%). CONCLUSION: A breath test significantly demonstrated greater oxidative stress in women with preeclampsia than in uncomplicated pregnancy and nonpregnant control subjects. The breath test accurately identified women with established preeclampsia, but further studies are required to determine if this test can predict the onset of disease.     

DLX4在子痫前期胎盘组织的表达及与上皮细胞间质化相关性的研究

目的:探讨DLX4在妊娠期高血压疾病中的作用及其对滋养细胞EMT的影响。方法:采用Western blot法分别检测子痫前期胎盘组织及缺氧培养的滋养细胞系JEG-3中DLX4蛋白表达的变化;通过实时PCR技术,比较缺氧条件下滋养细胞中DLX4、HIF-1α和E-cad表达变化的差异。结果:滋养细胞缺氧培养后DLX4蛋白表达明显下降(P0.05),与其在子痫前期胎盘组织的表达变化一致;缺氧抑制滋养细胞中DLX4 mR-NA表达,同时伴有HIF-1α和E-cad mRNA表达增加。结论:缺氧引起滋养细胞DLX4表达下调,伴随EMT相关因子表达的改变。子痫前期滋养细胞侵袭力异常可能与缺氧引起DLX4表达下调及滋养细胞EMT异常有关。     

Susceptibility of red blood cell lipids to in vitro oxidation and antioxidant status in preeclampsia

Objective

To investigate susceptibility of red blood cell (RBC) lipids to oxidation and antioxidant status in preeclampsia.

Study design

Twenty-one women with mild preeclampsia, 21 women with severe preeclampsia, and 20 healthy pregnant women were included in this cross-sectional study. Susceptibility of RBC to oxidative stress was determined by measuring RBC-malondialdehyde levels after incubation with hydrogen peroxide. Vitamins E and C, total carotenoids and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) activities and serum total antioxidant capacity (TAC) were determined spectrophotometrically. One-way analysis of variance and correlation analysis were used for statistical analyses.

Results

Compared with the normal pregnant women, susceptibility of RBC to oxidation was enhanced in the mild (p < 0.05) and severe (p < 0.01) preeclampsia groups, TAC was lower in the mild (p < 0.01) and severe (p < 0.001) preeclampsia groups. Vitamin C level was decreased in severe preeclampsia and total carotene level was decreased in mild and severe preeclampsia groups (p < 0.05). GPx activity was also decreased in the mild (p < 0.01) and severe (p < 0.05) preeclampsia groups.

Conclusion

The results of the present study supported the oxidative stress hypothesis of preeclampsia and it is possible that RBC play a role in the pathophysiology of the disease.