重度子痫前期与长链脂肪酸氧化酶基因蛋白表达异常的相关性

目的 探讨重度子痫前期与参与长链脂肪酸氧化的长链三羟基酰基辅酶A脱氢酶(LCHAD)mRNA和蛋白表达异常的相关性.方法 通过体外无血清培养胎盘滋养细胞,然后分为4组,分别用正常妊娠孕妇(NP组)、早发型重度子痫前期(E-PE组)、晚发型重度子痫前期(L-PE组)、重度子痫前期伴发HELLP综合征(HEILP组)患者血清刺激胎盘滋养细胞.采用实时荧光定量PCR和蛋白印迹法检测各组LCHAD基因和蛋白的表达.结果 (1)LCHAD的mRNA表达变化:NP、E-PE、L-PE及HELLP组LCHAD mRNA相对表达量分别为1.00±0.00、3.08±0.22、1.62±0.23、3.36±0.18.与NP组比较,E-PE、L-PE及HELLP组LCHAD的mRNA相对表达量均明显降低(P＜0.05);与L-PE组相比较,E-PE、HELLP组LCHAD的mRNA相对表达量也有明显降低(P＜0.05);而E-PE与HELLP组两组间LCHAD的mRNA表达差异无统计学意义(P＞0.05).(2)LCHAD蛋白表达变化:NP、E-PE、L-PE及HELLP组LCHAD/β-肌动蛋白比率分别为4.94±0.02、2.93±0.13、4.14±0.06、2.80±0.09.与NP组比较,E-PE、L-PE及HELLP组LCHAD蛋白表达均明显降低(P＜0.05);E-PE、HELLP组LCHAD蛋白表达比L-PE组都有明显降低,差异有统计学意义(P＜0.05);而E-PE与HELLP组两组间差异无统计学意义(P＞0.05).结论 重度子痫前期对胎盘滋养细胞中LCHAD的基因蛋白表达异常存在一定的影响,其中以早发型重度子痫前期和HELLP综合征的影响更为明显.脂肪酸氧化与子痫前期发生发展的相互影响和作用机制值得深入探讨.

Abstract：

Objective To explore the correlation between severe preeclampsia and abnormal expression of long-chain 3-hyroxyacyl-CoA dehydrogenase (LCHAD). Methods Serum-free trophoblast cells cultured in vitro were divided into 4 groups under the stimulations of normal pregnancy serum ( NP group), early onset severe preeclampsia serum (E-PE group), late onset severe preeclampsia serum (L-PE group) and HELLP ( hemolysis, elevated liver enzymes & low platelets) syndrome serum ( HELLP group)respectively. The expressions of mRNA and protein of LCHAD in trophoblast cells were detected by real-time polymerase chain reaction (PCR) and Western blot. Result ( 1 ) Expression of LCHAD mRNA: the relative expressions of mRNA of LCHAD in NP, E-PE, L-PE and HELLP groups were 1.00 ±0.00, 3.08 ±0.22, 1.62 ± 0. 23 and 3.36 ± 0. 18 respectively. The relative expressions of LCHAD mRNA were significantly reduced in the E-PE, L-PE and HELLP groups versus the NP group ( P ＜ 0. 05 ). Compared with the L-PE group, the gene expressions of LCHAD significantly decreased in the E-PE and HELLP groups (P ＜0.05 ) while no significant difference was found between the E-PE and HELLP groups (P ＞ 0. 05 ).(2) Expression of LCHAD protein: the relative expressions of LCHAD protein were 4.94 ±0.02, 2.93 ±0. 13, 4. 14 ±0. 06 and 2.80 ±0.09 in the NP, E-PE, L-PE and HELLP groups respectively. The protein expressions of LCHAD were remarkably reduced in the E-PE, L-PE and HELLP groups versus the NP group (P ＜ 0.05 ). The expressions of LCHAD protein remarkably decreased in the E-PE and HELLP groups versus the L-PE group (P ＜0.05) while no significant difference was found between the E-PE and HELLP groups (P ＞ 0. 05 ). Conclusion Long chain fatty acid oxidation is involved in the pathogenesis and development of preeclampsia. The expressions of LCHAD gene and protein are remarkably affected by early onset severe preeclampsia and HELLP syndrome. The interacting mechanism and influence between fatty acid oxidation and the development of preeclampsia are worth further exploring.     

Expression and Influence of Galectin-3 on Missed Abortion

Objective To explore the influence of galectin-3 on missed abortion. Methods Forty cases of normal intrauterine early pregnancy were randomly divided into 2 groups： surgical abortion group （group A, n=20） and medical abortion group （group B, n =20）. The third group was missed abortion group （group C, n =20） with the gestational age less than 13 weeks. Serum was isolated from the blood samples, collected and used for ELISA quantification of galectin-3. Villus and decidua tissues were collected from the abortus for immunohistochemical examination and real-time fluorescence relative quantitative PCR. Results The level of galectin-3 in the serum was the lowest in missed abortion group （P〈0.05）. Immunohistochemistry showed that galectin-3 expression in villus of missed abortion group was significantly lower than that of surgical abortion group （P〈0. 01）. Real-time fluorescence relative quantitative PCR showed that galectin-3 mRNA relative expression in villus of missed abortion group （2^-△△Ct=0. 04± 0. 01） was significantly lower than that of surgical abortion group （2^-△△Ct=1.00 ± 0.00）. Galectin-3 mRNA relative expression in deciduas of medical abortion group （2-zact=o. 08 ± 0.02） was s!gnificantly lower than that of surgical abortion group （2^-△△Ct=1.00 ± 0.00） （P〈0. 01）. Conclusion Galectin-3 is related to the development of villus and decidua during early pregnancy. The decreased expression of galectin-3 may promote the occurrence of missed abortion.     

Prostasin gene polymorphism at rs12597511 is associated with severe preeclampsia in Chinese Han women

Background Preeclampsia,characterized by hypertension and proteinuria,is a multifactorial disease associated with shallow invasion of trophoblast cells and inadequate spiral artery remodeling.Trophoblast and tumor cells have similar invasion mechanism.Prostasin is closely related to tumor development,invasion and metastasis and influences blood pressure through activating epithelial sodium channel.The effect of prostasin on the pathogenesis of preeclampsia remains unclear.This study investigated the association of prostasin gene at rs12597511 with severe preeclampsia.Methods A single nucleotide polymorphism,rs12597511,was tested with polymerase chain reaction and restrictionfragment length polymorphism analyses in 179 severe preeclampsia patients and 222 normal pregnant women.Results The frequencies of TC ＋ CC genotypes were significantly higher in severe preeclampsia group compared with in control group （the adjusted odds ratio was 2.030,95% confidence interval 1.195-3.449,P=0.009）.The C allele of rs12597511 was present significantly more often among women with severe preeclampsia （P=0.001）.Genotyping analysis showed that the C allele of rs12597511 could confer a risk for severe preeclampsia.Conclusion The higher frequency of C allele of prostasin gene at rs12597511 is associated with severe preeclampsia.     

Effects of Integrative Chinese and Western Medicine on Arterial Oxygen Saturation in Patients with Severe Acute Respiratory Syndrome

Objective: To evaluate the effects of treatment of integrative Chinese and Western medicine (ICWM) on arterial oxygen saturation (SaO2) in patients with severe acute respiratory syndrome (SARS). Methods:The non-randomized, controlled trial was conducted on 447 SARS patients treated synchronously with western conventional treatment (WM group, n = 171) alone and ICWM (ICWM group, n = 276). The changes of the cases with normal level (≥95% ) or abnormal level (<95% ) SaO2 were observed dynamically. Results: In the 3rd-14th day of the therapeutic course, the percentage of patients with normal SaO2 in the ICWM group was higher than that in the WM group (OR = 0.5178, P = 0.0038), and this tendency was more evident in patients of the severe type (OR = 0. 18, P = 0. 0001). However, the statistical significance of difference was only shown in patients for whom the ICWM treatment started in the early period after the onset (≤7 days after it, OR = 0.3803, P = 0.006), but not shown in those who received ICWM treat     

Outcome and risk factors of early onset severe preeclampsia

Background  Early onset severe preeclampsia is a specific type of severe preeclampsia, which causes high morbidity and mortality of both mothers and fetus. This study aimed to investigate the clinical definition, features, treatment, outcome and risk factors of early onset severe preeclampsia in Chinese women.

Methods  Four hundred and thirteen women with severe preeclampsia from June 2006 to June 2009 were divided into three groups according to the gestational age at the onset of preeclampsia as follows: group A (less than 32 weeks, 73 cases), group B (between 32 and 34 weeks, 71 cases), and group C (greater than 34 weeks, 269 cases). The demographic characteristics of the subjects, complications, delivery modes and outcome of pregnancy were analyzed retrospectively.

Results  The systolic blood pressure at admission and the incidence of severe complications were significantly lower in group C than those in groups A and B, prolonged gestational weeks and days of hospitalization were significantly shorter in group C than those in groups A and B. Liver and kidney dysfunction, pleural and peritoneal effusion, placental abruption and postpartum hemorrhage were more likely to occur in group A compared with the other two groups. Twenty-four-hour urine protein levels at admission, intrauterine fetal death and days of hospitalization were risk factors that affected complications of severe preeclampsia. Gestational week at admission and delivery week were also risk factors that affected perinatal outcome.

Conclusions  Early onset severe preeclampsia should be defined as occurring before 34 weeks, and it is featured by more maternal complications and a worse perinatal prognosis compared with that defined as occurring after 34 weeks. Independent risk factors should be used to tailor the optimized individual treatment plan, to balance both maternal and neonatal safety.

     

Expression of Toll-like receptor 4 in neonatal cord blood mononuclear cells in patients with preeclampsia

The expression of Toll-like receptor 4 (TLR4) in neonatal cord blood mononuclear cells (MNCs) and serum TNF-α were investigated in order to explore the roles of TLR4 in the pathogenesis of preeclampsia.The study enrolled 27 patients suffering from preeclampsia (experimental group) and 21 normal pregnancy patients (control group).After MNCs were separated, the expression of TLR4 mRNA and protein was detected by using real-time quantitative PCR and Western blotting respectively, and the expression of TNF-α by using ELISA.The results showed the TLR4 mRNA level in cord blood MNCs (2-CT:0.07±0.17), TLR4 protein expression level (absorbance ratio:0.81%±0.15%) and TNF-α level (9.5±1.73 pg/mL) were all increased in experimental group as compared with control group with the differences being statistically significant (P<0.05).There was a positive correlation between the expression of TLR4 mRNA and TNF-α in both experimental group and control group (r=0.54 and 0.53, respectively, P<0.05).It was concluded that TLR4 expression in the experimental group of cord blood MNCs was increased and there was a positive correlation between the expression of TLR4 mRNA and TNF-α in both groups.TLR4-mediated release of inflammatory cytokines may be one of the important reasons leading to preeclampsia.     

Expression of AIF-1 and RANTES in Unexplained Spontaneous Abortion and Possible Association withAlloimmuneAbortion

Objective To investigate the effects of allograft inflammatory factor-1 (AIF-1) and (RANTES) in sera and deciduas on unexplained early spontaneous abortion. Methods AIF-1 and RANTES were examined in sera and deciduas/endometria of 43 unexplained early spontaneous abortion women (group A), 40 healthy women with early pregnancy(group B) and 20 healthy women with no pregnancy (group C). Immu- nohistochemistry and enzyme linked immunosorbent assay (ELISA) were used in this study. Results AIF-1 protein was expressed both in deciduas of group A and in endometria of group C. In group A, H scores in the recurrent abortion deciduas specimens were significantly greater than those in the first abortion;in endometrium, expression of AIF-1 was greater in the secretory than in proliferative phase of group C. In group B, concentrations of RANTES in sera were higher in 7th-8th week of pregnancy than in 6th-7th and >8th week of pregnancy; expression of AIF-1 protein showed a negative correlation with RASNTES concentration; a significant increase of the RANTES levels in sera and tissue was observed in group B. Conclusion These results demonstrate, for the first time, that AIF-1 are expressed in deciduas of unexplained spontaneous abortion suggesting that AIF-1 involve in alloimmune abortion; RANTES might act as a novel blocking antibody;AIF-1 and RANTES might act as reliable markers for diagnosis of early alloimmune abortion.     

Effect of Lipoxin A4 on IL-1β Production of Monocytes and Its Possible Mechanism in Severe Preeclampsia

This study examined in vitro effect of lipoxin A 4 (LXA 4) on interleukin-1β (IL-1β) production of monocytes and its possible mechanism in severe preeclampsia (PE).Peripheral venous blood was drawn from 15 patients with severe preeclampsia (PE group) and 20 normal pregnant women (control group) to prepare monocytes which were then treated with LXA 4 at different concentrations of 0,10,100 nmol/L respectively.IL-1β level in the supernatant of monocytes was detected by enzyme linked immunoassay.The [Ca 2+ ] i of monocytes was measured by laser scanning confocal microscopy.The results showed that the IL-1β level and the [Ca 2+ ] i of monocytes in the PE group were significantly higher than those in the control group.LXA 4 significantly decreased the generation of IL-1β in a dose-dependent manner in the PE group.After treatment with 100-nmol/L LXA 4,in the PE group,the [Ca 2+ ] i concentration of monocytes was significantly reduced.It was concluded that LXA 4 may inhibit the IL-1β production of monocytes from severe preeclampsia women by inhibiting extracellular calcium influx.     

促纤溶物质膜联蛋白A2及其抗体在子痫前期中的变化及其临床意义

目的探讨促纤溶物质膜联蛋白A2(annexin A2)及其抗体在子痫前期患者外周血及胎盘组织中表达及临床意义,为子痫前期的抗凝治疗提供依据。方法通过酶联免疫吸附试验、聚合酶链式反应,Western Blot和免疫组化等方法,测定30例轻度子痫前期组、30例重度子痫前期组及30例正常妊娠组外周血和胎盘组织中annexin A2表达水平及外周血中的膜联蛋白A2抗体(anti-annexin A2)的表达水平。结果 3组受检者外周血和胎盘组织中annex-in A2的表达水平比较,差异均有统计学意义(P<0.05);与正常妊娠组比较anti-annexin A2在子痫前期的患者外周血中表达增强,差异有统计学意义(P<0.05)。结论子痫前期患者外周血和胎盘组织中annexin A2水平及其抗体表达水平的变化与子痫前期的发病有关。annexin A2和anti-annexin A2的表达变化可为子痫前期患者的临床抗凝治疗提供依据。     

早发型子痫前期孕妇血清及尿液中胎盘蛋白13的变化

目的 研究子痫前期孕妇血清及尿液中的胎盘蛋白13 （placentalprotein 13,PP13）的水平变化与早发型子痫前期的关系,以及对子痫前期发病的预测价值.方法 采用酶联免疫吸附（ELISA）法分别检测14例早发型子痫前期重度孕妇、18例晚发型子痫前期重度孕妇和16例正常妊娠孕妇血清及尿液中PP13的含量.结果 早发型子痫前期重度组和晚发型子痫前期重度组的血清及尿液中PP13含量高于正常对照组（P＜0.05）;同时,早发型子痫前期重度组的血清及尿液中PP13含量高于晚发型子痫前期重度组（P＜0.05）.结论 重度子痫前期孕妇血清及尿液中PP13水平高于正常妊娠孕妇,早发型重度子痫前期孕妇血清及尿液中PP13浓度均显著高于晚发型,且PP13含量随子痫前期病情加重而逐渐升高.     

尼卡地平联合硫酸镁对早发型重度子痫前期患者血液流变学及子宫血流动力学指标的影响

目的探讨尼卡地平联合硫酸镁对早发型重度子痫前期患者血液流变学及子宫血流动力学指标的影响。方法选取2009年1月～2011年10月于我院进行治疗的66例早发型重度子痫前期患者为研究对象,将其随机分为对照组（硫酸镁组）33例和观察组（尼卡地平联合硫酸镁组）33例,将两组患者治疗前及治疗后1、3 d的血液流变学及子宫血流动力学指标进行检测及比较。结果治疗后1 d及3 d观察组血液流变学及子宫血流动力学指标均低于对照组,差异均有统计学意义（均P〈0.05）。结论尼卡地平联合硫酸镁可显著降低早发型重度子痫前期患者的血液流变学及子宫血流动力学指标,对于改善疾病状态有明显的作用。     

早发型重度子痫前期108例临床分析

目的探讨早发型重度子痫前期的特点以及对妊娠结局的影响。方法选择2008年1月～2009年12月住院分娩的108例重度子痫前期孕妇的临床资料,按发病孕周将患者分为两组：48例孕周≤32周为早发型重度子痫前期组,60例孕周〉32周为晚发型重度子痫前期组。结果各组孕妇并发症发生率、新生儿窒息以及胎儿窘迫发生率比较,差异均有统计学意义（P〈0．05）。结论早发型重度子痫前期发病早、病情重,对母婴危害大,严密监测母儿情况、适当延长孕周、剖宫产是早发型重度子痫前期的主要分娩方式。     

早发与晚发型重度子痫前期的临床对比探析

目的探析早发型与晚发型重度子痫前期在临床治疗中的各项情况,如母体并发症、妊娠终止时机、围产儿结局等。方法对该院2009年3月—2012年5月收治的238例重度子痫前期患者的临床资料进行回顾性对比分析。结果早发型重度子痫前期患者的舒张压和收缩压显著高于晚发型重度子痫前期患者;早发型重度子痫前期患者的HELLP综合征、胎盘早剥、低蛋白血症、产后出血、眼底病变、肝损害的发生率均显著高于晚发型重度子痫前期患者;早发型重度子痫前期患者的胎死宫内、胎儿窘迫、新生儿轻、新生儿畸形、重度窒息的发生率显著高于晚发型重度子痫前期患者。结论早发型重度子痫前期和晚发型重度子痫前期在并发症、妊娠终止时机、围产儿结局等方面是存在差异的,在临床治疗中应当对症治疗。     

血栓调节蛋白在早发型重度子疒间前期患者胎盘组织中的表达

目的：探讨血栓调节蛋白（ thrombomodulin , TM）在早发型重度子疒间前期患者胎盘组织中的表达及其在发病中的作用。方法选择2012年1月到2013年2月在徐州市妇幼保健院产科住院分娩的重度子疒间前期患者60例,其中,早发型重度子疒间前期患者30例（早发型组）,晚发型重度子疒间前期患者30例（晚发型组）;选择同期健康早产产妇23例（早产组）,健康足月妊娠产妇30例（对照组）。应用反转录-聚合酶链反应（RT-PCR）检测各组产妇胎盘组织TM mRNA的表达水平。结果 TM mRNA在各组胎盘组织中均有表达,但表达程度有差异。早发型组与早产组、晚发型组、对照组比较差异均有统计学意义（ P＜0．05）;晚发型组与早产组、对照组比较差异均无统计学意义（P＞0．05）。结论早发型与晚发型重度子疒间前期可能存在不同的发病机制,TM可能在早发型重度子疒间前期的病理生理过程中起一定作用。     

43例早发型重度子痫前期期待治疗的临床分析

目的探讨早发型重度子痫前期期待治疗对母婴预后的影响。方法回顾分析43例早发型重度子痫前期患者,根据其发病孕周分为3组：A组孕周〈28周,B组孕周28～31＋6周,C组孕周32～34周,比较3组患者期待治疗的平均时间,并发症和围生儿结局。结果早发型重度子痫前期3组患者并发症发生率差异无统计学意义（P〉0.05）,新生儿病死率和围生儿病死率随着发病孕周的延长及治疗时间的延长而显著降低（P〈0.05）。结论早发型重度子痫前期严重影响母婴预后,适当期限内保守治疗有助于改善母儿结局。     

早发型重度子痫前期病情评估及处理的疗效分析

目的探讨采用早发型重度子痫前期病情评估表进行母胎病情评估分级,并启动相应监护、治疗方案的临床意义。方法选择我院收治的早发型重度子痫前期患者162例,根据住院卡号随机单盲分为研究组（单号）88例和对照组（双号）74例。研究组入院即按早发型重度子痫前期病情评估表进行母胎病情评估：分级并启动相应的监护、治疗方案进行治疗,治疗中均加用低分子肝素改善胎盘微循环,促胎儿生长;对照组按传统方法解痉、降压,必要时扩容、利尿处理,适时终止妊娠。比较两组治疗效果、孕产妇并发症、围生儿发病率和死亡率等情况。结果研究组与对照组患者延长孕龄天数、凝血功能改善、脐血流S／D值、产妇总并发症发生率、围生儿发病率和死亡率比较,差异有统计学意义（P〈0．05）。结论早发型重度子痫前期期待治疗中病情将逐渐加重,为母婴安全,采用早发型重度子痫前期病情评估表动态整体评估病情、指导治疗、适时终止妊娠有积极意义。     

重度子痫前期并发HELLP综合征影响因素分析

目的 探讨重度子痫前期并发HELLP(hemolysis,elevated liver enzymes and low platelet)综合征的影响因素,为预防减少HELLP综合征的发生提供临床资料。 方法 选取金华市人民医院2007年1月-2017年6月收治的182例重度子痫前期患者,根据术后是否发生HELLP综合征,分为HELLP组及非HELLP组,对可能发生HELLP综合征的相关因素进行分析,并对具有统计学意义的指标,进行多因素Logistic回归分析。 结果 182例重度子痫前期患者中发生HELLP综合征者36例,其发生率为19.78%。单因素分析及多因素Logistic回归分析显示:早发型子痫前期(OR=3.533,P=0.012,95%CI:1.421~9.744)、高龄产妇(OR=4.995,P=0.003,95%CI:1.671~10.651)是重度子痫前期并发HELLP综合征发生的独立危险因素。规律产检(OR=0.241,P<0.001,95%CI:0.080~0.721)是重度子痫前期并发HELLP综合征发生的保护因素。 结论 HELLP综合征是重度子痫前期的并发症之一,而对高龄产妇及早发型子痫前期患者更应该规律产检,筛查高危因素,以降低HELLP综合征的发生率。      

早发型重度子痫前期患者胎盘组织M-CSF、CRH和HO-2表达的研究

目的：研究早发型重度子痫前期患者胎盘组织中巨噬细胞集落刺激因子(MCSF)、促肾上腺皮质激素释放激素(CRH)、血红素氧化酶-2(HO-2)的表达,探讨它们在早发型重度子痫前期发病机制中的作用。方法整群选择选自2013年9月—2014年8月在郑州大学第三附属医院住院的孕妇73例,年龄22~37岁,孕周32~37周。早发型重度子痫前期患者25例,晚发型重度子痫前期患者23例,正常妊娠对照组25例进行实验对照研究,应用免疫组化方法研究M-CSF、CRH、HO-2的表达情况。结果①三期组孕妇之间年龄、终止妊娠孕周比较,差异均无统计学意义(P﹥0.05)(见表1)。②与正常妊娠组比较,早发型及晚发型重度子痫前期组M-CSF表达水平均明显升高;早发型组M-CSF表达水平明显高于晚发型组。③与正常妊娠组比较,早发型及晚发型组CRH表达水平均明显升高;早发型组CRH表达水平明显高于晚发型组。④与正常妊娠组比较,早发型及晚发型组HO-2表达水平均明显降低;早发型组HO-2表达水平低于晚发型组,差异无统计学意义(P﹥0.05)。结论胎盘中MCSF、CRH的表达增加和HO-2表达降低可能与早发型重度子痫前期的发病有关。