胎盘MDR3的表达及其与妊娠期肝内胆汁淤积症关系的研究

目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)胎盘中胆盐载体磷脂输出泵(multidrug resistance p-plycoprotein,MDR3)的表达,以及母、胎血中总胆汁酸(total bile acids,TBA)和甘胆酸(cholylglycine,CG)水平的变化;进一步分析胎盘胆盐载体对胆汁酸水平的调节作用及其与ICP的关系。方法ICP(ICP组)及正常妊娠(对照组)孕妇各20例。母血、胎儿脐静脉血中TBA、CG水平的测定分别采用放射免疫法和速率法;胎盘组织中胆盐载体MDR3 mRNA的表达采用荧光定量PCR法。结果(1)ICP组母血、脐血中的TBA、CG水平均高于对照组(P<0.05)。ICP组母血TBA水平高于脐血(25.8±16.6和8.6±5.5)μmol/L,CG水平高于脐血(3416.1±1986.0和821.8±673.2)μg/dL(P<0.05);对照组母血和脐血TBA水平(3.4±2.5和4.4±3.3)μmol/L,CG水平(342.7±234.9和309.3±145.2)μg/dL比较,差异无统计学意义(P>0.05)。(2)ICP和正常妊娠各期胎盘组织中均有MDR3 mRNA的表达。ICP组MDR3 mRNA表达量低于对照组(0.80±0.67和162.63±334.33)拷贝/ng(P<0.05)。(3)ICP组、对照组胎盘中MDR3 mRNA表达量与母血、脐血中TBA和CG水平均无相关性(r=-0.60~0.165,P>0.05)。结论ICP胎盘胆盐载体MDR3 mRNA表达降低,可能引起ICP胎盘对胆汁酸的转运障碍、胎儿体内胆汁淤积,可能是引起ICP胎儿窘迫的原因。     

妊娠期肝内胆汁淤积症儿缺氧脑损伤的研究

目的:探讨妊娠期肝内胆汁淤积症(ICP)患者胆汁酸水平、胎儿缺氧与胎儿脑损伤的关系.方法:选择2006年3月至9月在我院诊治的ICP患者(ICP组)及正常孕妇(正常妊娠组)各30例.采用彩色多普勒超声检测胎儿大脑中动脉收缩期峰值流速/舒张末期流速(S/D)、阻力指数(RI);用全自动生化分析仪测定母血及新生儿脐动脉血清胆汁酸(BA)、乳酸、和pH值;采用酶联免疫吸附试验(ELISA法)测定新生儿脐动脉血清神经元特异性烯醇化酶(NSE)浓度,并对两组的结果进行分析和比较.结果:①ICP组母血及脐血BA水平均高于正常妊娠组(P<0.01),并且ICP组母血与脐血BA呈正相关关系(r=0.937,P<0.01).②ICP组脐血乳酸水平和NSE值均高于正常妊娠组(P<0.01);而ICP组脐血pH值、大脑中动脉血流S/D值、RI值均低于正常妊娠组(P<0.01);ICP组脐血NSE浓度分别与队、乳酸水平呈正相关(P<0.01);与砌值、大脑中动脉血流S/D值及脐血pH值呈负相关(P<0.01).结论:ICP胎儿存在缺氧和脑损伤,ICP胎儿脑损伤与胎儿缺氧及高浓度胆汁酸密切相关,对ICP患者胎儿大脑中动脉血流和脐动脉血pH值、乳酸浓度及NSE的联合检测,可早期诊断ICP胎儿缺氧,早期发现新生儿脑损伤.     

血红素氧合酶/一氧化碳体系在妊娠期肝内胆汁淤积症的表达及意义

目的:探讨妊娠肝内胆汁淤积症(ICP)患者的血红素氧合酶/一氧化碳(HO/CO)体系变化意义及其与胎儿预后的关系。方法:采用双波长分光光度计法测定25例ICP患者及25例正常晚孕妇女母血、脐血血浆CO的含量;用免疫组化法测定两组孕妇胎盘组织中HO-2蛋白的相对表达量;用免疫组织化学SABC法确定血红素氧合酶(HO)在体外分离培养人胎盘滋养层细胞上的表达及定位。结果:(1)ICP组母血血浆CO的含量为33.0±10.9μmol/L,与对照组的含量为38.3±6.1μmol/L相比,差异有统计学意义(P<0.05);(2)ICP组脐血血浆CO的含量为26.7±7.0μmol/L,与对照组的含量31.1±7.7μmol/L相比,差异有统计学意义(P<0.05);(3)ICP组母血血浆CO的含量与TBA相关,(r=-0.32,P<0.005);(4)未发现ICP组CO水平与羊水粪染、胎儿出生体重、Apgar评分、脐动脉S/D值及孕周之间相关;(5)ICP组胎盘组织中HO-2蛋白定量结果为OD=0.88±0.41,与对照组的OD=1.24±0.47相比,差异有统计学意义(P<0.05);(6)HO在体外分离培养人胎盘滋养层细胞有表达,阳性物质分布于胞浆内,胞核为阴性反应。结论:(1)ICP患者母血血浆和脐血血浆CO的水平降低,胎盘组织中HO-2表达减少。HO/CO体系与ICP的发生发展及患者胎儿的不良结局有关;(2)HO在体外分离培养人胎盘滋养层细胞有表达,阳性物质分布于胞浆内,胞核为阴性反应。     

妊娠肝内胆汁淤积症孕妇及其新生儿血清总胆酸水平变化对胎儿心脏功能的影响

目的 探讨妊娠肝内胆汁淤积症(ICP)孕妇及其新生儿脐动脉血(脐血)血清总胆酸(TBA)水平变化对胎儿心脏功能的影响.方法 应用循环酶法测定30例ICP孕妇(ICP组)及30例正常妊娠妇女(对照组)外周静脉血及其新生儿脐血TBA水平,单克隆夹心酶联免疫法测定新生儿脐血心肌肌钙蛋白I(cTnI)水平,用彩色多普勒超声诊断仪测定胎儿左心室Tei指数.结果 (1)TBA:ICP组孕妇血清TBA水平为(36.0±9.6)μmol/L,新生儿脐血TBA水平为(10.1±2.0)μmol/L;分别高于对照组的(3.8±0.9)、(5.5±0.4)μmol/L,差异均有统计学意义(P<0.01),且ICP组孕妇血清TBA水平明显高于其分娩的新生儿脐血TBA水平,两者比较,差异有统计学意义(P<0.01),对照组孕妇血清TBA水平明显低于其分娩的新生儿脐血TBA水平,两者比较,差异也有统计学意义(P<0.01).(2)Tei指数:ICP组胎儿左心室Tei指数为0.58±0.04,明显高于对照组的0.43±0.03,差异有统计学意义(P<0.01).(3)cTnI:ICP组新生儿脐血cTnI水平为(0.92±0.23)μg/L,明显高于对照组的(0.52±0.10)μg/L,差异也有统计学意义(P<0.01).(4)ICP组脐血TBA水平与孕妇血清TBA、脐血cTnI水平及胎儿左心室Tei指数均呈正相关关系(r=0.769、0.635、0.758,P<0.01);脐血cTnI水平与胎儿左心室Tei指数呈正相关关系(r=0.637,P<0.01).结论ICP胎儿存在左心室功能异常及心肌损伤,这种损伤可能与孕妇血TBA水平升高有密切关系;胎儿左心室Tei指数可作为监测ICP胎儿心脏功能及心肌损伤程度的指标.     

妊娠期高血压疾病孕妇血及脐血中抑制素及表皮生长因子水平的变化

目的探讨妊娠期高血压疾病孕妇血及其分娩的新生儿脐血血浆中抑制素(INH)和表皮生长因子(EGF)的水平变化及其对妊娠期高血压疾病发病及胎儿生长发育的影响。方法采用酶联免疫吸附试验(ELISA),检测65例妊娠期高血压疾病患者(观察组)及21例正常妊娠妇女(对照组)及其分娩的新生儿脐血血浆中INH、EGF水平。结果观察组孕妇血浆INH水平为(499±52)ng／L,对照组为(421±36)ng／L,两组比较,差异有统计学意义(P<0．01)。观察组新生儿脐血INH水平为(274±53)ng／L,对照组为(252±28)ng／L,两组比较,差异无统计学意义(P>0．05)。观察组EGF水平为(408±60)ng／L,对照组为(463±87)ng／L,两组比较,差异有统计学意义(P< 0．05)。观察组新生儿脐血中EGF水平为(232±99)ng／L,对照组为(380±97)ng／L,两组比较,差异也有统计学意义(P<0．01)。脐血中EGF水平与新生儿体重呈正相关关系(r=0．326,P<0．05),与胎盘重量呈正相关关系(r=0．451,P<0．05)。结论孕妇血浆中INH、EGF水平与妊娠期高血压疾病的发病有关,脐血中EGF水平对胎儿及胎盘的生长发育有影响。     

妊娠肝内胆汁淤积症患者高水平胆汁酸对血管内皮细胞生长因子的作用

目的　探讨妊娠肝内胆汁淤积症 (ICP)患者高水平胆汁酸对血管内皮细胞生长因子(VEGF)的作用及其与胎儿窘迫的关系。方法　采用酶联免疫吸附试验 (ELISA)法测定 3 3例ICP产妇(ICP组 )和 3 0例正常晚期妊娠妇女 (对照组 )血清中VEGF水平 ;采用免疫组织化学方法测定两组产妇的胎盘血管密度 ;采用放射免疫法测定两组产妇的血清胆汁酸水平。结果　 (1)ICP组产妇的VEGF水平为 (2 0 72± 17)ng/L ,胆汁酸水平为 (47 9± 14 2 )ng/L ,血管密度为 (68± 5 )个 /高倍镜下 ;对照组产妇VEGF水平为 (2 2 5 6± 3 0 )ng/L ,胆汁酸水平为 (1 6± 0 7)ng/L ,血管密度为 (74± 7)个 /高倍镜下。 (2 )ICP组产妇血清中VEGF水平与胆汁酸水平呈负相关 ,与胎盘血管密度呈正相关。对照组产妇血清中VEGF水平与胆汁酸水平无相关性 ,与胎盘血管密度呈正相关。结论　ICP产妇血清中高水平的胆汁酸对血管内皮细胞具有细胞毒性作用 ,导致内皮细胞分泌VEGF减少 ,造成ICP患者胎盘毛细血管减少 ,母儿间物质交换困难。这可能是ICP患者易发生胎儿窘迫及胎死宫内的原因之一。     

妊娠肝内胆汁淤积症患者的胎儿淋巴细胞研究

目的探讨胎儿淋巴细胞在妊娠肝内胆汁淤积症(ICP)发病中的作用。方法采用单向混合淋巴细胞反应法,检测20例ICP患者(ICP组)及20例正常孕妇(对照组)的脐血胎儿淋巴细胞与母体外周血已灭活的淋巴细胞、皮肤组织可溶性抗原、蜕膜组织可溶性抗原的增殖反应情况。结果(1)ICP组脐血胎儿淋巴细胞与母体已灭活的淋巴细胞混合反应中,胎儿淋巴细胞的增殖反应程度为2．75±0．36,显著高于对照组的1．45±0．19,两组比较,差异有统计学意义(P＜0．05);(2) ICP组脐血胎儿淋巴细胞与母体蜕膜组织可溶性抗原混合反应中,胎儿淋巴细胞的增殖反应程度为1．45±0．19,显著高于对照组的0．67±0．24,两组比较,差异有统计学意义(P＜0．05);(3)ICP组脐血胎儿淋巴细胞与母体皮肤组织可溶性抗原反应中,胎儿淋巴细胞的增殖反应程度为1．22±0．44,显著高于对照组的0．66±0．27,两组比较,差异有统计学意义(P＜0．05)。结论胎儿淋巴细胞可能是ICP发病过程中的主要效应细胞之一;母-胎间免疫失衡是ICP发病的重要机制之一。     

妊娠期肝内胆汁淤积症胎儿监护与围生儿预后关系分析

目的:探讨对妊娠期肝内胆汁淤积症(ICP)孕妇进行胎儿监护的临床价值。方法:对223例ICP孕妇进行无负荷试验(NST),其中89例进行缩宫素激惹试验(OCT),所有孕妇均进行超声脐动脉血流分析及肝功能检测。结果:OCT和超声脐血流分析结果异常者的围生儿预后不良发生率分别为63.89%和21.43%,明显高于正常者的16.98%和11.11%(P<0.05,P<0.05)。NST正常者和异常者的围生儿预后不良发生率无明显差异。ICP患者的胎儿窘迫、新生儿窒息、早产、胎儿电子监测异常及脐血流异常高于正常组。ICP组中总胆汁酸大于50μmol/L组的胎儿电子监护异常及脐血流S/D值异常的发生率,均高于其他两组。结论:OCT和超声脐动脉血流分析对了解ICP孕妇胎盘功能和预测围生儿预后具有较高的临床价值。     

GDM孕妇血清晚期糖基化终产物水平与其胎儿出生缺陷的关系及临床意义

目的:检测妊娠期糖尿病(GDM)孕妇血清及脐血血清中晚期糖基化终产物(AGE)的水平,并观察胎盘组织中AGE受体(RAGE)的表达,探讨AGE与胎儿出生缺陷的关系及其在产前筛查中的临床意义。方法:选择经产前筛查诊断为胎儿畸形或胎死宫内的GDM孕妇作为病例组(42例),随机选择GDM无胎儿异常孕妇作为GDM组(30例),无妊娠合并症的健康孕妇作为健康对照组(30例)。采用酶联免疫法检测孕妇血清及脐血血清AGE水平;采用免疫组化方法检测胎盘组织中RAGE蛋白的表达。结果:病例组、GDM组、健康对照组脐血血清AGE水平分别为(223.9±54.6),(160.7±37.2),(108.3±15.8)μg/L,三组差异显著(P<0.05);病例组、GDM组、健康对照组孕妇血清AGE水平分别为(169.1±14.3),(105.4±17.2),(80.6±11.4)μg/L,三组亦有显著差异(P<0.05);病例组孕妇血清与脐血血清中AGE水平呈正相关(r=0.863,P<0.01);病例组、GDM组及健康对照组胎盘组织中RAGE的阳性表达率分别为87.5%、53.1%、29.6%,三组差异显著(P<0.05)。结论:GDM孕妇高AGE血症是导致出生缺陷的危险因素,孕妇血清AGE水平可作为GDM出生缺陷的产前筛查指标。     

胎儿窘迫孕妇静脉血及脐血中内源性阿片肽水平的测定

目的　探讨内源性阿片肽与胎儿窘迫发生的关系。方法　采用放射免疫法测定 40例正常妊娠妇女 (正常妊娠组 )及 43例胎儿窘迫孕妇 (胎儿窘迫组 )静脉血及其新生儿脐血中阿片肽 (β 内啡肽、强啡肽A1 13和亮啡肽 )的水平 ,胎儿窘迫组孕妇同时行新生儿脐动脉血血气分析。结果　 (1)胎儿窘迫组脐血中 β 内啡肽、强啡肽A1 13和亮啡肽的水平分别为 (45 3± 68)ng/L、(2 42± 3 3 )ng/L及(498± 68)ng/L ;正常妊娠组分别为 (2 5 1± 3 9)ng/L、(10 3± 2 2 )ng/L及 (3 2 2± 40 )ng/L。与正常妊娠组比较 ,胎儿窘迫组脐血中 3种阿片肽水平均显著升高 (P <0 0 5 )。 (2 )胎儿窘迫组脐血血气分析结果 :pH为 (7 0± 0 1) ,PO2 为 (1 7± 0 6)kPa ,PCO2 为 (8 9± 0 7)kPa ;其中 β 内啡肽水平与脐血pH、PO2呈显著负相关 [相关系数 (r)为 - 0 418及 - 0 43 7,P <0 0 1],与PCO2 呈显著正相关 (r =0 44 2 ,P <0 0 1) ;强啡肽A1 13水平与脐血pH及PO2 呈负相关 (r为 - 0 3 3 7及 - 0 3 83 ,P <0 0 5 ) ,与PCO2 呈正相关 (r=0 3 46,P <0 0 5 )。 (3 )胎儿窘迫组孕妇血中 β 内啡肽、强啡肽A1 13和亮啡肽水平分别为(40± 13 )ng/L、(64± 16)ng/L及 (2 19± 40 )ng/L ;正常妊娠组分别为 (3 7± 9)ng/L、(5     

胎儿脑电图及其定量分析用于产时胎儿窘迫诊断的研究

目的探讨胎儿脑电图(fetal electroencephalogram,FEEG)波形及其定量分析用于产时诊断胎儿窘迫及判断新生儿预后的价值。方法采用自制的经阴道胎儿脑电电极对65例产妇在第一产程末至胎儿娩出前进行FEEG监测,观察脑电图波形变化并进行定量分析;并将胎儿窘迫组(22例)和非胎儿窘迫组(43例)的脑电图波形及定量分析结果进行比较。同时比较胎儿酸中毒组和血气正常组两组的脑电图波形,分析新生儿近期预后与产时FEEG关系。结果(1)应用经阴道直接接触胎儿头皮的脑电电极记录的脑电图与新生儿脑电图特点相似;(2)胎儿窘迫组产时脑电图波形异常率明显高于非胎儿窘迫组(72·7%和9·0%,P<0·05),前者双频指数(bispectral index,BIS)明显降低、95%边缘频率(spectral edge frequency,SEF)明显升高;(3)胎儿酸中毒组与血气正常组相比产时脑电图及其定量分析有显著异常(BIS:48·23±1·98和70·18±0·76,P<0·05;95%SEF:29·02±1·09和14·02±1·69,P<0·01);(4)产时FEEG异常与新生儿不良预后有关。结论(1)自制的经阴道胎儿脑电电极可准确地采集胎儿脑电信号,且不损伤胎儿头皮,是安全、可行的;(2)胎儿脑电波异常可较早的反映胎儿宫内缺氧及酸中毒的状况,并可做为产时胎儿监测的直观指标;(3)产时胎儿脑电图定量分析BIS、95%SEF是反映胎儿和新生儿缺氧及酸中毒的敏感指标。     

Antepartum fetal evaluation by assessment of fetal heart rate and fetal movements

Three antenatal monitoring tests--fetal movement acceleration test (FMAC-test), fetal heart rate-nonstress test (FHR-NST), and daily fetal movement recording (DFMR) were evaluated in 212 high risk pregnant women. While in 196 cases all three tests were normal, in 16 patients one to three tests showed pathological results. In the latter group, there was a significantly higher incidence of perinatal mortality, low Apgar score and growth retardation. Since false positives are known to occur in these tests, at least two should be pathological to warrant delivery in am attempt to prevent fetal death in utero. The sequence in which the pathology appears in the deteriorating fetus is as follows: the first to become non-reactive is the FMAC-test, followed by decreased fetal movements till cessation, and, finally, severe changes in the FHR-NST take place. The importance of this sequence of events is discussed.     

Open fetal surgery for life-threatening fetal malformations

After more than two decades of experimental and clinical work, fetal surgery has become an accepted treatment modality for selected fetuses with life-threatening anomalies. Color Doppler ultrasound and ultrafast fetal magnetic resonance imaging have enhanced the accuracy of prenatal evaluation traditionally made by ultrasound alone. Fetal lung masses associated with hydrops are nearly 100% fatal. These lesions can be resected in utero if they are predominantly solid or multicystic. Thoracoamniotic shunting may be effective in the setting of a single large predominant cyst. Fetuses diagnosed with left congenital diaphragmatic hernia before 26 weeks' gestation with liver herniation and a sonographic right lung to head circumference ratio (LHR) of less than one may benefit from fetal tracheal occlusion. Fetal sacrococcygeal teratoma complicated with placentomegaly, hydrops, or progressive high output heart failure may benefit from in utero resection of the tumor. Although preterm labor still remains the Achilles heel of open fetal surgery, effective tocolysis may, in the future, expand the scope of fetal surgery.     

Transient fetal hypothyroidism due to direct fetal administration of amiodarone for drug resistant fetal tachycardia

Amiodarone, an anti-arrhythmic drug that contains 39% iodine, is rarely known to cause negative effects on fetal thyroid function after gestational exposure, when given orally to a pregnant woman. Two cases of fetal hypothyroidism after gestational exposure to amiodarone by direct fetal intravenous route are described here.     

Evaluation of fetal movements with ultrasonic Doppler fetal actograph

Fetal movements in each trimester were recorded objectively and continuously with an ultrasonic Doppler actograph that enables simultaneous tracing of fetal heart rate (FHR) and fetal movement (FM). The record with this method was compared with those of the ultrasonic B-mode and M-mode respectively. The onset of FM signal bursts and FHR acceleration was nearly synchronous and the transitory FHR increase associated with FM signal bursts showed a linear amplitude increment along with the progress of gestation. Fetal hiccup movements were recorded from 24 weeks of gestation and lasted between 4.3 minutes and 17 minutes with a rate of 25 to 28 per minute. No FHR acceleration was recognized in such movements. Maternal perception was 67.7% on average of FM signal bursts. Fetal movements in early pregnancy were detected in the 11th week of gestation (CRL 54 mm). Long-term recording of fetal movements was carried out between 9:30 and 17:00 and the alternation of active and resting phases was investigated. The resting phase lasted 20 minutes on average, (range, 10 to 36 minutes). The fetal activity was not influenced by the maternal food intake. It is clinically significant to evaluate the change in fetal movements objectively and continuously.