干扰素-γ诱导蛋白10在子痫前期大鼠模型的表达

目的:检测子痫前期孕鼠子宫及胎盘中干扰素-γ诱导蛋白10(IP-10)的表达,探讨其与子痫前期发病的关系。方法:采用注射L-NAME方法制备子痫前期动物模型,将妊娠大鼠随机分为正常妊娠组、子痫前期组。同时采用免疫组化及Western blot法检测IP-10在正常妊娠组、子痫前期组孕鼠肝脏、肾脏、子宫及胎盘等组织中的表达。结果:免疫组化及Western blot结果显示在子痫前期组,孕鼠肝脏、肾脏中IP-10表达增加,与正常妊娠组差异有统计学意义(P<0.05)。正常妊娠组孕鼠子宫及胎盘IP-10表达不明显,而子痫前期组孕鼠子宫及胎盘IP-10表达大幅增高,差异有统计学意义(P<0.05)。同样在子痫前期组中,胎盘中IP-10表达量显著高于子宫中IP-10的表达量,两者差异有统计学意义(P<0.05)。结论:子痫前期孕鼠子宫及胎盘IP-10表达升高可能与子痫前期的发病有关。     

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。     

白介素24在子痫前期胎盘的表达及与基质金属蛋白酶2关系的研究

目的:研究IL-24在子痫前期胎盘的表达及rhIL-24对TEV-1细胞MMP-2蛋白活性表达的影响,探讨二者与子痫前期发病机制的关系。方法:RT-PCR检测子痫前期及正常足月孕妇胎盘中IL-24 mRNA的表达;明胶酶谱检测0、10、50、100、500ng/mlrhIL-24作用后TEV-1细胞的MMP-2活性;Western blot检测不同浓度rhIL-24作用后TEV-1细胞的MMP-2蛋白表达。结果:子痫前期组胎盘组织中IL-24 mRNA表达显著高于正常足月组(P<0.05)。当rhIL-24浓度≥50ng/ml后,TEV-1细胞中MMP-2蛋白活性表达均明显降低(P<0.05),并呈一定的浓度依赖性。结论:IL-24异常升高,抑制了滋养细胞MMP-2的分泌及活性,使其侵袭力下降,从而在子痫前期发病中起一定作用。     

血清可溶性Fas与胎盘组织胎盘生长因子的表达在早发型重度子痫前期发病中的作用

目的:探讨血清可溶性Fas与胎盘组织胎盘生长因子在早发型重度子痫前期发病中的作用。方法:采用ELISA和免疫组化法分别检测20例早发重度子痫前期患者、35例晚发重度子痫前期患者和40例正常晚期妊娠患者血清可溶性Fas(Soluble Fas,sFas)和胎盘组织胎盘生长因子(placental growth factor,PlGF)的表达。结果:正常妊娠组、早发重度组、晚发重度组血清sFas水平分别为(1.17±0.53)、(6.68±0.97)和(3.17±0.74)mg/L,早发重度组、晚发重度组均显著高于正常对照组,差异有显著性(P<0.05)。早发重度组又明显高于晚发重度组,差异有显著性。正常妊娠组胎盘组织PlGF表达的平均灰度值显著高于早发型及晚发型重度子痫前期组,其中早发型子痫前期重度组表达最低。早发重度组中血清sFas与PlGF呈负相关,相关系数-0.748。结论:重度子痫前期患者血清sFas表达升高,且早发重度组表达显著高于晚发重度组,并与PlGF呈负相关,说明其异常表达可能是早发重度子痫前期发病的主要原因。     

Hemodynamic characteristics in preeclampsia women during cesarean delivery after spinal anesthesia with ropivacaine

BACKGROUND Very few studies have been published on the hemodynamic changes associated with spinal anesthesia induced with ropivacaine during cesarean deliveries in preeclamptic women.AIM To record and analyze hemodynamic data in women with preeclampsia undergoing cesarean delivery after spinal anesthesia induced with ropivacaine.METHODS Ten eligible women with preeclampsia were enrolled in this prospective observational study.Spinal anesthesia was performed with 2.4 mL of 0.5%ropivacaine.Hemodynamic changes were then analyzed at multiple time points.The hemodynamic responses to vasopressor interventions and uterotonic agents,as well as maternal and neonatal outcomes were also recorded.RESULTS Stable hemodynamic trends were observed in this study.Cardiac output(CO)and stroke volume increased mildly during surgery.In contrast,mean arterial pressure and systemic vascular resistance showed a moderate decrease from induction until the end of surgery.Central venous pressure dramatically increased after delivery.Oxytocin administration was associated with the most significant hemodynamic fluctuations during surgery,namely,an increase in CO and heart rate.Phenylephrine intervention was only required in three patients,and caused an increase in mean arterial pressure and systemic vascular resistance along with a decrease in heart rate,stroke volume,and CO.No maternal and neonatal complications were observed during this study,except transient episodes of hypotension.CONCLUSION Spinal anesthesia for caesarian delivery with ropivacaine in women with preeclampsia is linked to modest hemodynamic changes of no clinical significance in this study.Careful cardiovascular monitoring is still recommended,particularly after the delivery of the fetus or the use of oxytocin.     

Effect of nicotine on placental ischemia-induced complement activation and hypertension in the rat

Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia. Nicotine, a major component of cigarettes, stimulates the efferent cholinergic anti-inflammatory pathway through peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to attenuate ischemia–reperfusion injury in kidney and liver. Prior studies indicated that complement activation was critical for placental ischemia-induced hypertension in a rat model. Thus, it was hypothesized here that nicotine was responsible for the protective effect of cigarette smoking in preeclampsia and would attenuate placental ischemia-induced systemic complement activation and hypertension. The Reduced Utero-placental Perfusion Pressure (RUPP) model in the pregnant rat was employed to induce placental ischemia, resulting in complement activation, fetal resorptions, and hypertension. On gestation day (GD)14, nicotine (1?mg/kg) or saline was administered via subcutaneous injection prior to RUPP surgery and daily through GD18. On GD19, placental ischemia significantly increased mean arterial pressure (MAP) in saline injected animals. However, the placental ischemia-induced increase in blood pressure was not evident in nicotine-treated animals and nicotine treatment significantly increased MAP variability. Circulating C3a was measured as an indicator of complement activation and increased C3a in RUPP compared to Sham persisted with nicotine treatment, as did fetal resorptions. These data suggested to us that nicotine may contribute to the decreased risk of preeclampsia with cigarette smoking, but this protective effect was confounded by additional effects of nicotine on the cardiovascular system.     

子痫前期合并睡眠呼吸暂停患者血清白细胞介素18的改变及持续气道正压通气干预疗效

目的 观察子痫前期合并阻塞性睡眠呼吸暂停(OSA)患者的血清IL-18水平,通过持续气道正压通气(CPAP)观察IL-18的改变.方法 纳入2008年8月至2010年8月常州市妇幼保健医院行多导睡眠监测(PSG)及常规孕期体检的妊娠妇女,孕期24～40周,年龄23～40岁,其中AHI＜5次/h的健康妊娠妇女18名(健康对照组),AHI＜5次/h的子痫前期患者18例(单纯子痫组),AHI≥5次/h的子痫前期患者16例(子痫合并OSA组),其中6例AHI≥15次/h,行持续气道正压通气(CPAP)治疗1周(治疗组).采用ELISA法测定血清IL-18水平并比较各组及治疗前后的差异.结果 健康对照组、单纯子痫组及子痫合并OSA组血清IL-18水平为(261±95)、( 382±121)和(601±89) ng/L,各组间差异均有统计学意义(均P＜0.01).治疗组患者CPAP治疗后,AHI、收缩压及血清IL-18水平均降低,最低脉氧饱和度明显升高(均P＜0.01),舒张压明显下降(P＞0.05).结论 子痫前期合并OSA患者IL-18水平较高,提示OSA可能诱导和加重机体更强的炎症反应而增加子痫前期的发病率,经CPAP治疗有效.     

Baseline placental growth factor levels for the prediction of benefit from early aspirin prophylaxis for preeclampsia prevention

ObjectivePlacental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin.Study designSecondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60 mg/d (n = 102) or placebo (n = 72), with PlGF collected at 13 w 0 d–16 w 6 d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders.ResultsROC analysis indicated 87.71 pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p = 0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p = 0.445).ConclusionsUnlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated.CondensationHigh-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin.     

Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis

Objectives

MTHFR C677T and A1298C have been associated with the risk of preeclampsia (PE), but with conflicting results. We performed this meta-analysis to derive a more precise estimation of the association between MTHFR polymorphisms and PE.

Study design

An electronic search of PubMed and Chinese Biomedicine database was conducted to select studies for meta-analysis. 54 case controlled studies containing MTHFR C677T and A1298C gene polymorphisms were chosen, and odds ratio (OR) with confidence interval (CI) was used to assess the strength of this association.

Result

These studies evaluated 7398 cases and 11230 controls for MTHFR C677T. The overall results suggested that MTHFR C677T was associated with the risk of PE. (T vs. C: OR = 1.157, 95 % CI: 1.057-1.266, p=0.002; TT+CT vs. CC: OR=1.165, 95 % CI : 1.049-1.293, P = 0.004; TT vs. CT + CC: OR = 1.371, 95 % CI: 1.153-1.63, p < 0.001). We also evaluated 1103 cases and 988 controls for MTHFR A1298C but could not demonstrate an increased risk of PE for this polymorphism (p=0.667). A symmetric funnel plot, the Egger’s test (p = 0.819) suggested a lack of publication bias.

Conclusion

This meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk for PE, especially in the case of Asians and Caucasians.     

The effect of maternal hypertension on mortality in infants 22, 29 weeks gestation

ObjectiveTo evaluate the effect of maternal hypertension on mortality risk prior to discharge, in infants 22 + 0 to 29 + 6 weeks gestational age.Study designWe evaluated 88,275 North American infants whose births were recorded in Vermont Oxford Network centers between 2008 and 2011 Infants born between 22 + 0 and 29 + 6 weeks gestational age were evaluated in 2-week gestational age cohorts and followed until death or discharge. Logistic regression was used to adjust for birth weight, antenatal steroid exposure, infant sex, maternal race, inborn/outborn, prenatal care and birth year.Results21,896 infants were born to hypertensive mothers; 13% died prior to Neonatal Intensive Care Unit discharge compared to 20% of the 66,379 infants born to mothers without hypertension. After adjustment, infants had significantly lower mortality compared to preterm infants not born to hypertensive mothers, at all gestational ages examined (22/23: odds ratio (OR) = 0.65 (95% Confidence Interval (CI): 0.55, 0.77; 24/25); OR = 0.77 (95% CI: 0.71, 0.84); 26/27: OR = 0.66 (95% CI: 0.59, 0.74); 28/29: OR = 0.58 (95% CI: 0.51, 0.67). Additionally, births associated with maternal hypertension increase dramatically by gestational age, resulting in a larger proportion of births associated with maternal hypertension at later gestational ages.ConclusionsPreterm birth due to any cause carries significant risk of mortality, especially at the earliest of viable gestational ages. Maternal hypertension independently influences mortality, with lower odds of mortality seen in infants born to hypertensive mothers, after adjustment, and should be taken into consideration as an element in counseling parents.