胎盘及外周血中STBM与早发型重度子痫前期病因的研究

目的:测定孕妇胎盘组织和血清合体滋养细胞层微绒毛膜(STBM)在重度子痫前期的表达情况,揭示早发型与晚发型重度子痫前期可能具有不同的病因及发病机制.方法:收集在我院治疗的早发型与晚发型重度予痫前期患者各15例,及与两组孕周相匹配正常妊娠孕妇各10例.采用实时荧光定量PCR(Real-time RT-PCR)方法测重度子痫前期患者胎盘中STBM的标记物TPAmRNA水平,另用酶联免疫分析法(ELLSA)测定血清和胎盘中STBM的标记物TPA蛋白表达水平.结果:①早发型组孕妇胎盘STBM的标记物TPA相对含量(2.04±0.32 ng/ml),高于晚发型组(1.75±0.31 ng/ml)(P＜0.05),早发型组胎盘STBM的标记物TPA mRNA含量(0.0342±0.0021)高于晚发组(0.0222±0.0020)(P＜0.05);②早发型组孕妇血清中STBM的标记物TPA水平(1.88±0.43 n#m1)高于晚发型组(1.59±0.26 ng/ml)(p＜0.05).早发型组和晚发型组血清中STBM的标记物TPA水平均高于同期正常孕妇血清中的TPA水平(P均＜0.05).③早发型组孕妇胎盘组织中STBM的标记物TPA水平与血清尿素氮水平、血清肌酐水平、S/D比值之间均呈显著正相关.晚发型组中与血清肌酐水平之间呈显著正相关.④早发型组孕妇血清中STBM的标记物TPA水平与血清肌酐水平、收缩压、舒张压之间均呈显著正相关.晚发型组中与血清肌酐水平、S/D比值、收缩压之间均呈显著正相关.结论:早发型重度子痫前期胎盘的合体滋养细胞凋亡早且严重,早发型与晚发型重度子痫前期可能具有不同的病因及发病机制.     

氧化低密度脂蛋白及其受体与子痫前期发病的关系

目的 探讨氧化低密度脂蛋白(oxLDL)及血凝集素样氧化低密度脂蛋白受体1(LOX-1)与子痫前期发病的关系.方法 选择2007年6月至2008年1月在青岛大学医学院附属医院产科住院分娩的子痫前期孕妇73例,其中轻度子痫前期孕妇35例(轻度子痫前期组),重度子痫前期孕妇38例(重度子痫前期组).选取同期正常晚期妊娠妇女45例为对照组.采用酶联免疫吸附试验检测各组孕妇血浆中oxLDL水平;采用RT-PCR、蛋白印迹法分别检测各组孕妇胎盘组织中LOX-1 mRNA及蛋白表达水平;采用RT-PCR检测各组孕妇胎盘组织中半胱氨酸天门冬氨酸蛋白酶-3(caspase-3)mRNA表达水平.结果 (1)轻度及重度子痫前期组孕妇血浆中oxLDL水平分别为(0.42±0.11)及(0.68±0.12)mg/L,明显高于对照组的(0.35±0.14)mg/L,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(2)轻度及重度子痫前期组孕妇胎盘组织中LOX-1mRNA表达水平分别为0.70±0.10及0.84±0.08,明显高于对照组的0.58±0.11,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(3)轻度及重度子痫前期组孕妇胎盘组织中LOX-1蛋白表达水平分别为0.79±0.15及0.90±0.12,明显高于对照组的0.68±0.11,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(4)轻度及重度子痫前期组孕妇胎盘组织中caspase-3 mRNA表达水平分别为3.82±0.18及5.39±0.14,明显高于对照组的2.19±0.20,差异有统计学意义(P<0.01);重度子痫前期组又明显高于轻度子痫前期组(P<0.01).(5)轻度及重度子痫前期组孕妇血浆中oxLDL水平与胎盘组织中LOX-1 mRNA表达水平呈正相关(r=0.93,P<0.05);胎盘组织中LOX-1 mRNA表达与胎盘组织caspase-3 mRNA表达水平呈正相关(r=0.84,P<0.05).结论 子痫前期孕妇血浆中oxLDL水平升高,并上调胎盘组织中的LOX-1表达水平,从而参与子痫前期的病理生理过程.     

子痫前期孕妇血清、胎盘组织MMP-9及NGAL表达变化及其意义的研究

目的:探讨孕妇血清基质金属蛋白酶-9(MMP-9)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平变化及胎盘组织中MMP-9mRNA、NGAL mRNA表达变化在子痫前期发病中的作用.方法:选取60例重度子痫前期孕妇,按发病时孕周不同分为早发型组(发病孕周≤34周)和晚发型组(发病孕周＞34周)各30例;另选30例正...     

胎盘组织中血凝素样氧化低密度脂蛋白受体1和凋亡相关基因的表达与子痫前期发病的关系

目的 探讨胎盘组织中血凝素样氧化低密度脂蛋白受体1(LOX-1)和凋亡相关基因easpase-3、Bax及bcl-2的表达及其与子痫前期发病的关系.方法 选择2005年6月-2006年12月在中国医科大学附属盛京医院产科住院的子痫前期患者30例(子痫前期组),以同期正常孕妇40例为对照组.采用免疫组化、RT.PCR技术和蛋白印迹(western-blot)法检测两组孕妇不同孕周胎盘组织中LOX-1和caspase-3、Bax及bel-2的表达.结果 (1)子痫前期组20周+1～24周、24周+1～28周、28周+1-32周、32周+1～36周、36周+1～40周孕妇胎盘组织中LOX-1蛋白表达水平分别为20.1±1.8、25.6±1.3、32.8±1.6、34.3±1.5、39.9±1.2,对照组分别为11.2±0.6、18.5±1.6、26.1±1.8、28.3±1.6、32.3±1.6,两组分别比较,差异均有统计学意义(P<0.05);子痫前期组孕妇胎盘组织中easpase-3蛋白表达水平分别为12.3±0.9、16.3 4-0.9、24.4±0.8、28.3±0.5、36.3±1.1,对照组分别为8.5±1.0、12.3±1.1、17.4±1.2、20.4±0.5、24.2±1.3,两组比较,差异均有统计学意义(P<0.05).(2)子痫前期组不同孕周孕妇胎盘组织中LOX-1、easpase-3及Bax mRNA和蛋白的表达水平明显高于对照组,两组比较,差异有统计学意义(P<0.05);bel-2 mRNA和蛋白的表达趋势与Bax表达结果相反.结论 LOX-1和caspase-3、Bax在子痫前期患者胎盘组织中表达上调,bcl-2表达下调,-与子痫前期发病有关.     

重度子痫前期患者胎盘合体滋养细胞凋亡的研究

目的 比较早发型与晚发型重度子痫前期患者胎盘合体滋养细胞凋亡水平变化,探讨其病因及发病机制的差异.方法 选择2008年11月至2009年5月在上海交通大学附属第六人民医院住院剖宫产分娩的早发型重度子痫前期患者15例(早发型组)、晚发型重度子痫前期患者15例(晚发型组)和健康妊娠妇女10例(对照组),采用酶联免疫吸附试验检测孕妇血浆中合体滋养细胞微粒(STBM)水平,蛋白印迹法检测胎盘组织中凋亡蛋白--半胱氨酸天冬氨酸蛋白酶3(caspase-3)蛋白表达水平.结果 (1)STBM:早发型组孕妇血浆STBM水平为(71±21)μg/L,高于晚发型组的(42±30)μg/L和对照组的(26±11)μg/L,分别比较,差异均有统计学意义(P＜0.05);晚发型组血浆STBM水平与对照组比较,差异无统计学意义(P＞0.05).(2)caspase-3蛋白:早发型组胎盘组织中caspase-3蛋白表达水平为0.85±0.61,晚发型组为0.77±0.46,对照组为0.32±0.15,早发型和晚发型组胎盘组织中caspase-3蛋白表达水平均高于对照组,差异有统计学意义(P＜0.05);但早发型组和晚发型组比较,差异无统计学意义(P＞0.05).结论 早发型与晚发型重度子痫前期可能存在不同的发病机制,早发型重度子痫前期可能是一种胎盘疾病,而晚发型则可能与母体因素有关.     

子痫前期孕妇血清中氧化应激产物H_2O_2对sHLA-G表达的影响

目的:探讨子痫前期患者血清中氧化应激产物H2O2对可溶性人类白细胞抗原G(sHLA-G)表达的影响,分析早发型及晚发型子痫前期的病因。方法:选择早发型和晚发型子痫前期孕妇各15例为研究组,以同期正常孕妇15例为对照组。采用比色法及ELISA法分别检测3组研究对象血清中H2O2含量和sHLA-G表达,并进行相关性分析。结果:(1)早发型及晚发型子痫前期组孕妇血清中H2O2呈高水平表达[(58.43±3.56)μmol/L,(29.84±7.67μmol/L)],与正常妊娠组相比[(21.61±4.25)μmol/L],差异均有统计学意义(P均<0.05);早发型子痫前期组孕妇血清中H2O2含量显著高于晚发型子痫前期组(P<0.05)。(2)早发型及晚发型子痫前期组孕妇血清中sHLA-G呈低水平表达[(28.65±9.16)U/ml,(51.84±8.67)U/ml],与正常妊娠组[(98.13±13.26)U/ml]相比,差异有统计学意义(P均<0.05);早发型子痫前期组孕妇血清中sHLA-G表达量显著低于晚发型子痫前期组(P<0.05)。(3)正常妊娠、子痫前期孕妇血清中的H2O2水平与sHLA-G表达呈负相关(r=-0.835,P<0.05)。结论:早发型子痫前期发病早,受氧化应激损伤更严重,血清中sHLA-G表达量更低;氧化应激产物H2O2可能潜在下调sHLA-G表达,与子痫前期发病及病情轻重程度相关。     

三维能量彩色多普勒超声用于检测子痫前期孕妇胎盘组织血流灌注的价值

目的 探讨三维能量彩色多普勒超声检测子痫前期孕妇胎盘组织血流灌注的临床价值.方法 选择2007年7月至2008年5月在首都医科大学附属北京妇产医院超声科行产前超声检查的正常孕妇及子痫前期孕妇共80例,其中36例正常孕妇为正常孕妇组,44例子痫前期孕妇分为轻度子痫前期组(9例),重度子痫前期组(26例),慢性高血压合并子痫前期组(慢高合并子痫前期组,9例).应用三维能量彩色多普勒超声仪检测各组孕妇胎盘三维直方图血管指数(VI)、血流指数(FI)、血管化血流指数(VFI),应用二维多普勒超声检测脐血流收缩期/舒张期血流速度峰值(S/D值).并记录分娩孕周、新生儿出生体重、低出生体重儿百分比和胎盘重量.结果 (1)VI、FI、VFI及脐血流S/D值:正常孕妇组分别为6.3±2.9、38.6±4.4、2.7±1.3及2.5±0.6;轻度子痫前期组分别为5.7±3.8、36.3±7.2、2.4±2.0及2.4±0.3;重度子痫前期组分别为3.0±2.4、31.7±5.0、1.1±1.0及2.9±1.3;慢高合并子痫前期组分别为2.2±1.6、26.1±4.4、0.8±0.6及3.1±1.6.正常孕妇组孕妇胎盘VI、FI、VFI值与轻度子痫前期组比较,差异均无统计学意义(P>0.05),而重度子痫前期组和慢高合并子痫前期组孕妇胎盘VI、FI 、VFI兀值均明显低于正常孕妇组(P<0.01)及轻度子痫前期组(P<0.05).而各组孕妇脐血流S/D值相互比较,差异均无统计学意义(P>0.05).(2)分娩孕周、新生儿出生体重、低出生体重儿百分比和胎盘重量:正常孕妇组分别为(38.7±1.5)周、(3280±520)g、3%及(568±141)g;轻度子痫前期组分别为(37.9 ±1.0)周、(2971±265)g.0及(576±98)g;重度子痫前期组分别为(33.2±2.6)周、(1820±737)g.58%及(458±154)g;慢高合并重度子痫前期组分别为(32.6±2.6)周、(1497±533)g.7/9及(396±141)g.正常孕妇组与轻度子痫前期组分娩孕周、新生儿出生体重、低出生体莺儿百分比和胎盘重量比较,差异均无统计学意义(P>0.05),而重度子痫前期组和慢高合并重度子痫前期组的分娩孕周、新生儿出生体重、低出生体重儿百分比和胎盘重量均明显低于正常孕妇组(P<0.01)与轻度子痫前期组(P<0.05).结论 (1)重度子痫前期及慢高合并子痫前期孕妇胎盘组织的血流灌注明显减少,临床上相应出现胎盘重量及新生儿出生体重下降、分娩孕周偏低、低出生体重儿数量增加等结果;而脐血流S/D值无明显变化.(2)三维能量彩色多普勒超声对胎盘组织血流灌注的检测有重要的临床诊断意义.     

血清、脐血中MPO水平变化及胎盘组织MPO mRNA表达与子痫前期发病的关系

目的:研究重度子痫前期(PE)患者血清MPO及胎盘组织中MPO mRNA表达水平变化与PE发病的关系,探讨糖脂代谢异常及氧化应激在PE病理生理机制中的可能作用。方法:选取60例重度PE孕妇,按发病时孕周不同分为早发型PE组(孕周34周)和晚发型PE组(孕周≥34周)各30例。另选取同期健康晚期妊娠孕妇60例,分为对照1组(孕周34周)和对照2组(孕周≥34周)各30例。采用实时荧光定量PCR技术检测胎盘组织中MPO mRNA表达水平;ELISA法检测血清MPO水平。检测患者血压、血脂、血糖、胰岛素水平等指标,进行相关性分析。结果:PE组的血清MPO水平高于对照组(P0.05),且早发型高于晚发型PE组(P0.05);但对照组间比较无差异(P0.05)。PE组的血清TC、TG、LDL、FINS、HOMA-IR分别高于对照组(P0.05),HDL水平低于对照组(P0.05);但PE组间比较及对照组间比较,均无差异(P0.05)。PE组的脐血MPO水平、胎盘组织中MPO mRNA表达水平均高于对照2组(P0.05),且早发型高于晚发型组(P0.05)。PE组的血清MPO水平与TG、HoMA-IR、FINS、胎盘组织MPO mRNA表达水平均呈正相关(r=0.557、0.615;0.694、0.511;0.766、0.717;0.696、0.695),与血HDL呈负相关(r=-0.697,-0.576);对照2组则无相关性。结论:MPO可能参与了PE的病理生理过程。胎盘组织中MPO mRNA表达水平升高可能是血清MPO水平升高的重要原因。PE患者血脂代谢异常及胰岛素抵抗增加与血清MPO水平升高有关,它们可能参与了血清MPO水平升高后促发PE的氧化应激的病理生理过程。     

脂氧素A4、白三烯C4和5-脂氧合酶在重度子痫前期孕妇外周血中的表达及意义

目的 探讨脂氧素A4、白三烯C4和5-脂氧合酶在不同类型重度子痫前期孕妇外周血中的表达及其意义. 方法 收集2010年12月至2011年6月在本院产前检查并分娩的单胎妊娠孕妇共45例,其中正常妊娠组20例,早发型重度子痫前期组10例,晚发型重度子痫前期组15例.酶联免疫吸附试验测定血浆中脂氧素A4和白三烯C4的水平,实时荧光定量逆转录-聚合酶链反应技术检测外周血白细胞中5-脂氧合酶mRNA的表达水平,采用方差分析及LSD-t检验比较组间脂氧素A4、白三烯C4和5-脂氧合酶mRNA的差异,脂氧素A4、白三烯C4和5-脂氧合酶mRNA表达水平间的相关性采用直线相关分析. 结果 早发型和晚发型重度子痫前期组孕妇血浆脂氧素A4水平分别为(355.3±116.0)pg/ml和(389.7±117.5)pg/ml,均较正常妊娠组[(555.0±139.8) pg/ml]明显降低(t=-4.03和-3.77,P均＜0.05).白三烯C4水平在早发型、晚发型重度子痫前期组和正常妊娠组分别为(591.3±185.5) pg/ml、(510.3±197.1) pg/ml和(496.9±158.8) pg/ml,3组间差异无统计学意义(F=0.889,P＞0.05).白细胞中5-脂氧合酶mRNA表达水平在早发型、晚发型重度子痫前期组和正常妊娠组分别为4.8±2.0、4.4±1.2和4.2±1.9,3组间差异无统计学意义(F=0.311,P＞0.05).各组脂氧素A4、白三烯C4水平及5-脂氧合酶mRNA表达水平间均无相关性(P均＞0.05).结论 脂氧素A4早且明显降低可能参与早发型重度子痫前期的发生.     

神经激肽B和内皮素1与妊娠期高血压疾病发病的关系

目的 探讨神经激肽B(NKB)和内皮素1(ET-1)与妊娠期高血压疾病(HDCP)发病的关系.方法 选择2005年3-7月在华中科技大学同济医学院附属协和医院妇产科行产前检查的22例HDCP孕妇作为研究对象,其中,妊娠期高血压12例为妊娠期高血压组,子痫前期10例为子痫前期组;同期22例正常孕妇为对照组.分别采用酶联免疫吸附试验测定3组不同孕周孕妇血浆中NKB和ET-1的水平,采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接法(SP)检测NKB在胎盘组织中的定位和表达,采用RT-PCR技术检测胎盘组织中的NKB mRNA和ET-1 mRNA表达.结果 (1)子痫前期组孕10～14周、孕20～24周、孕30～34周孕妇血浆中NKB和ET-1的水平分别为(35.6±5.2)、(17.9±4.3)μg/L,(39.5±4.3)、(22.7±3.6)μg/L,(47.1±3.3)、(27.5±3.5)μg/L;对照组分别为(22.9±3.3)、(10.7±5.3)μg/L,(30.2±3.4)、(13.2±4.1)μg/L,(34.6±4.3)、(16.6±4.8)μg/L,两组分别比较,差异均有统计学意义(P<0.05);妊娠期高血压组与对照组比较,差异均无统计学意义(P>0.05).(2)各组孕妇胎盘组织中的绒毛合体滋养细胞、绒毛血管内皮细胞及间质细胞的胞质内均可观察到NKB蛋白阳性染色颗粒,其中以合体滋养细胞的分布为主.子痫前期组胎盘组织中的NKB蛋白表达水平(0.244±0.020)显著高于对照组(0.160±0.012),两组比较,差异有统计学意义(P<0.05).而妊娠期高血压组NKB蛋白表达水平(0.162±0.019)与对照组比较,差异无统计学意义(P>0.05).(3)子痫前期组孕妇胎盘组织中的NKB mRNA(0.97±0.36)和ET-1 mRNA(0.90±0.36)表达水平显著高于对照组(分别为0.78±0.54、0.65±0.47),两组比较,差异有统计学意义(P<0.05);而妊娠期高血压组(分别为0.80±0.40、0.70±0.32)与对照组比较,差异无统计学意义(P>0.05).(4)子痫前期组孕妇血浆中NKB水平与ET-1水平呈正相关关系(r=0.79,P<0.05).结论 子痫前期患者在孕早期(孕10～14周)临床症状出现之前,其血浆中NKB和ET-1水平即已显著升高,胎盘组织中NKB和ET-1表达水平也明显升高.子痫前期患者体内NKB和ET-1水平变化与HDCP的发病密切相关.     

Comparison of maternal and umbilical cord blood soluble lectin-like oxidized low-density lipoprotein receptor 1 levels in early- and late-onset preeclampsia

Background

The main purpose of this study was to determine the maternal and umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset preeclampsia (PE).

Materials and methods

A case–control study was conducted in pregnant women with early-onset (before 34 weeks’ gestation n = 19) and late-onset (after 34 weeks’ gestation n = 22) PE compared to healthy normotensive pregnant controls (n = 44). Groups were compared for the maternal and umbilical cord plasma oxLDL and serum sLOX-1 levels.

Results

The mean maternal and umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased in early- and late-onset PE compared to controls (p < 0.001). When early- and late-onset PE women were compared with serum sLOX-1 levels, the increase was more pronounced in early PE (p < 0.001). However, same comparison is not statistically significant in cord blood for oxLDL where as it is significantly higher in maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL and sLOX-1 levels are positively correlated with each other; however, they are negatively correlated with fetal weight and gestational age.

Conclusions

According to our results, maternal and umbilical cord blood levels of oxLDL and sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying than oxLDL for the differentiation of early and late preeclampsia.     

Comparison of angiogenic and anti-angiogenic factors in maternal and umbilical cord blood in early- and late-onset pre-eclampsia

Purpose: The aim of this study was to compare maternal and umbilical cord serum levels of the angiogenic and anti-angiogenic factors in early- and late-onset pre-eclamptic pregnancies as well as in normal pregnancies, which might have significant importance in the etiology of pre-eclampsia. Materials and Methods: This prospective case-control study was carried out with pre-eclamptic (early-onset, ≤?34 weeks and late-onset, >34 weeks) and normal pregnant women. VEGF, PIGF, sFlt-1 and sEng levels in maternal and umbilical cord serum were measured before delivery and the findings were compared. Results: The study was conducted with 15 early- and 15 late-onset pre-eclampsia patients, and 17 patients with normal pregnancies. It was found that sEng levels were higher in the umbilical cord serum in the early-onset and in the maternal serum in the late-onset pre-eclampsia group than the control group (p < 0.05). No significant difference in any factor was observed between the early- and late-onset pre-eclampsia groups. Conclusion: In this study, the results showed that angiogenic and anti-angiogenic factor levels in maternal serum and umbilical cord serum may not be related to the time of onset of pre-eclampsia.     

激活素A、Bax和XIAP在特发性胎儿生长受限患者的表达及意义

目的:探讨特发性胎儿生长受限(IFGR)患者母血和脐血激活素A(ActivinA)及胎盘组织中B细胞淋巴瘤因子相关x蛋白(Bax)和X-连锁凋亡抑制蛋白(XIAP)的表达及意义。方法:选取剖宫产分娩的IFGR孕妇30例作为实验组,同期因社会因素剖宫产分娩的正常足月孕妇30例作为对照组。采用双抗体夹心酶联免疫吸附法(ELISA)测定两组母血、脐血ActivinA水平;免疫组化法检测两组胎盘组织中Bax与XIAP的表达。结果:实验组母血、脐血ActivinA水平(102.659±16.467,57.752±13.498)ng/ml均明显高于对照组(75.927±10.519,29.870±5.992)ng/ml(P<0.05)。Bax、XIAP在胎盘合体滋养细胞中的表达,实验组Bax平均灰度值(146.513±10.611)明显高于对照组(113.672±9.631),差异有统计学意义(P<0.05);实验组XIAP平均灰度值(114.562±5.167)明显低于对照组(144.430±7.311),差异有统计学意义(P<0.05)。实验组母血、脐血中ActivinA水平与胎盘组织中Bax表达均呈正相关(P<0.05),与胎盘组织中XIAP表达均呈负相关(P<0.05);实验组胎盘组织中Bax表达与XIAP表达呈负相关(P<0.05)。结论:母血、脐血中ActivinA升高及胎盘组织中Bax表达增加、XIAP表达降低可能是IFGR发病的重要环节之一。在IFGR中ActivinA可能通过上调Bax的表达、下调XIAP的表达,促进胎盘滋养细胞过度凋亡,影响胎盘的发育和功能,进而影响胎儿生长发育。     

Comparison of interleukin-6 levels in maternal and umbilical cord blood in early- and late-onset preeclampsia

Purpose: Increased inflammatory response and cytokines are claimed to play a significant role in the etiology of preeclampsia. Interleukin-6 (IL-6) is a proinflammatory cytokine. Limited number of studies evaluating IL-6 levels in preeclamptic patients have produced conflicting results. Therefore, the present study sought to compare maternal and umbilical cord serum levels of IL-6 in early- and late-onset preeclamptic pregnancies as well as in normal pregnancies. Materials and methods: A total of 69 participants were enrolled in the study. The control group consisted of 24 participants with normal pregnancies. Preeclampsia group consisted of 45 participants. The preeclampsia group was further classified into the subgroups of early- and late-onset preeclampsia. Late-onset preeclampsia group consisted of 24 women whereas early-onset preeclampsia group consisted of 21 women. Serum and umbilical cord samples of IL-6 were compared. Results: There was no significant difference between maternal and umbilical cord serum IL-6 concentrations between the preeclampsia and control group. No significant difference was observed in maternal and umbilical cord serum IL-6 levels between early- and late-onset preeclampsia groups. Conclusion: Our results do not support an increase in IL-6 levels in patients with early- and late-onset preeclampsia. The clinical relevance of our findings needs to be further investigated.     

子痫前期孕妇血清与胎盘尿紧张素Ⅱ的表达及意义

目的:检测子痫前期孕妇外周血和新生儿脐血血清中尿紧张素Ⅱ(urotensinⅡ,UⅡ)水平和UⅡmRNA在胎盘组织的表达水平,探讨其在子痫前期发生发展中的作用。方法:(1)ELISA测定30例子痫前期患者及15例正常晚期妊娠孕妇(对照组)外周血和新生儿脐血血清UⅡ水平;(2)用RT-PCR法检测各组孕妇胎盘组织中UⅡmRNA的表达水平。结果:(1)重度子痫前期组孕妇外周血血清UⅡ水平明显高于轻度子痫前期组和对照组,差异均有显著性(P<0.05)。轻度和重度子痫前期组的脐静脉血清UⅡ浓度均明显高于对照组(P<0.05,P<0.001)。(2)胎盘组织UⅡmRNA表达水平在轻度和重度子痫前期组均明显高于对照组,差异有显著性(P<0.05)。结论:UⅡ可能参与子痫前期全身小血管痉挛的机制并在胎盘组织缺血缺氧和动脉粥样硬化的发生起重要作用。     

子痫前期患者血清脂联素表达水平与血脂代谢及胰岛素抵抗的相关性

目的:探讨脂联素、血脂代谢及胰岛素抵抗与子痫前期发病的关系。方法:选择2007年9月—2008年7月住院分娩的妊娠妇女120例及妊娠前健康体检妇女30例,其中60例子痫前期妊娠妇女按发病时妊娠周不同分为早发型组(29例,发病时妊娠周≤34周)和晚发型组(31例,发病时妊娠周>34周)。60例正常晚期妊娠妇女分为妊娠≤34周组和妊娠>34周组,各30例;采用酶联免疫吸附法(ELISA)检测各组血清脂联素与胰岛素水平;应用全自动生化分析仪测定血脂、血糖水平。检测临床相关指标,包括血压、妊娠前体质量等,并进行相关性分析。结果:①早发型子痫前期组血清脂联素低于同期对照组,晚发型子痫前期组血清脂联素低于同期对照组,差异均有统计学意义(P<0.05);且早发型组低于晚发型组,差异有统计学意义(P<0.05),校正红细胞压积(HCT)后,仍有统计学意义。②早发型、晚发型子痫前期组血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、载脂蛋白B(ApoB)、空腹胰岛素(FINS)水平及胰岛素抵抗指数(IRI)均高于同期对照组,而高密度脂蛋白(HDL)、载脂蛋白A1(ApoA1)低于同期对照组(均P<0.05)。③早发型、晚发型子痫前期组血清脂联素与TG、收缩压(SP)、舒张压(DP)、平均动脉压(MAP)及IRI均呈负相关;与HDL呈正相关。结论:子痫前期妊娠妇女血清脂联素表达降低可能与子痫前期发病有关;血脂代谢异常及胰岛素抵抗与子痫前期患者脂联素表达降低有关,可能参与低脂联素促发子痫前期的病理生理机制。     

Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely correlated with maternal circulating leptin

Introduction

miRNAs are small non-coding RNAs important for the regulation of mRNA in many organs including placenta. Adipokines and specifically leptin are known to be dysregulated in preeclampsia, but little is known regarding their regulation by miRNAs during pregnancy.

Methods

We performed high-throughput sequencing of small RNAs in placenta from 72 well-defined patients: 23 early-onset preeclampsia (PE), 26 late-onset PE and 23 controls. The regulation of some miRNAs was confirmed on qRT-PCR. Maternal circulating levels and placental mRNA of leptin, resistin and adiponectin were measured using Bio-Plex and qRT-PCR.

Results

We found that miR-1301, miR-223 and miR-224 expression was downregulated in early-onset PE, but not in late-onset PE, compared to controls. In silico analysis predicted the leptin gene (LEP) to be a target for all three miRNAs. Indeed, we found significant correlation between maternal circulating levels of leptin and placental LEP expression. In addition, we found a significant inverse correlation between maternal circulating leptin/placental LEP expression and placental miR-1301 expression levels. Interestingly, placental expression of miR-1301 was also correlated with newborn weight percentile and inversely correlated with both maternal systolic and diastolic blood pressure prior to delivery.

Discussion

Our results confirm that placenta is a major site of LEP expression during pregnancy. It further suggests that miR-1301 could be involved in the regulation of leptin during pregnancy and may play a role in early-onset PE.

Conclusions

miR-1301 is dysregulated in early-onset preeclampsia and could possibly play a role in the regulation of leptin during pregnancy.     

Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion

Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p?<?0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p?<?0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions. Conclusions: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE.