血清总胆汁酸和凝血指标与不良妊娠结局关系的多因素分析

目的探讨血清总胆汁酸(TBA)、凝血功能指标的变化与妊娠期胆汁淤积症(ICP)不良妊娠结局的关系。方法选取郑州大学附属郑州中心医院既往诊治的ICP孕妇144例作为研究对象进行回顾性分析,以孕妇是否出现不良妊娠结局作为分组标准,其中发生不良妊娠结局的61例作为不良组,未发生不良妊娠结局的83例作为对照组。结果不良组的血清TBA、FIB、D-D水平均高于对照组(P<0.05);不良组与对照组的血清AST、ALT、TBIL、DBIL、发病孕周比较,差异有统计学意义(P<0.05);Logistic回归模型结果显示:发病孕周越小、血清DBIL、TBA、FIB及D-D水平越高是ICP孕妇发生不良妊娠结局的独立危险因素(P<0.05)。结论ICP孕妇的血清TBA、FIB及D-D水平越高,其发生不良妊娠结局的风险将增大。     

妊娠急性脂肪肝11例早期诊治分析

目的 探讨妊娠急性脂肪肝(AFLP)的早期诊断方法和处理原则.方法 对四川大学华西第二医院2003年1月至2006年12月收治的11例AFLP病例进行回顾性分析.结果 (1)临床表现患者出现恶心、呕吐、厌食、乏力、黄疸等临床表现;(2)实验室检查肝功异常丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)轻到中度升高,总胆红素、直接胆红素明显升高,白蛋白降低;肾功异常肌酐、尿素氮明显升高;凝血功能障碍凝血酶原时间延长、血小板降低、DIC;其他部分患者白细胞增高,血糖降低;(3)影像学检查超声诊断AFLP9例.CT诊断AFLP2例;(4)孕产妇及围生儿结局孕产妇死亡1例;围生儿死亡1例.结论 早期诊断和及时终止妊娠,并加强支持疗法是治疗AFLP的关键,可有效降低母婴死亡率.     

妊娠合并恙虫病12例临床分析

目的:探讨妊娠合并恙虫病患者的临床特征及诊断治疗,为临床诊断和治疗提供参考依据。方法:对广东医学院附属医院收治的12例妊娠合并恙虫病患者的临床资料进行回顾性分析。结果:12例中10例为农村人口,6例在夏季发病。发热、焦痂(或溃疡)12例,头痛11例,全身酸痛6例,淋巴结肿大7例;血常规白细胞正常10例、血小板正常10例,外斐试验OX_K阳性1例;肝功能损害者[丙氨酸氨基转移酶(ALT)40 U/L或天门冬酸氨基转移酶(AST)40 U/L]8例。首诊误诊7例。治疗后均痊愈,11例胎儿正常。结论:妊娠合并恙虫病主要发生在夏秋季,多见于农村人口。常出现发热、头痛、焦痂等临床表现,多有轻度肝功能损害。首诊误诊率高。阿奇霉素治疗效果确切,对胎儿安全。     

胆汁酸、肝酶、α-羟丁酸脱氢酶水平对妊娠期肝内胆汁淤积症患者围产结局的预测价值

目的分析胆汁酸、肝酶、α-羟丁酸脱氢酶(α-HBDH)水平对妊娠期肝内胆汁淤积症(ICP)患者围产结局的预测价值。方法抽取河南省信阳市中心医院2012年1月至2017年6月住院分娩的ICP患者80例(观察组)及正常孕妇80例(对照组),检测两组孕妇血清总胆汁酸(TBA)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)及α-HBDH水平。依据TBA、肝酶指标将ICP分级,比较各组围产结局,并分析上述生化指标对妊娠结局的预测价值。结果观察组孕妇血清TBA、AST、ALT、α-HBDH水平均显著比对照组高(P0.05);中度组、重度组早产、羊水污染、低出生体重儿发生率均比对照组显著高(P0.05);重度组早产、羊水污染、低出生体重儿发生率均比轻度组显著高(P0.05);α-HBDH预测早产敏感度81.26%,TBA预测羊水污染敏感度89.05%;TBA、AST、ALT、α-HBDH预测低出生体重儿敏感度分别为80.18%、80.04%、80.01%、80.00%。结论 TBA、肝酶指标及α-HBDH对早产、低出生体重儿等妊娠结局预测敏感度均较高。     

血清总胆汁酸的测定在妊娠肝内胆汁瘀积症中的诊断意义

目的探讨血清总胆汁酸的测定在妊娠肝内胆汁瘀积症中的诊断意义与胎儿预后的关系.方法以病例对照研究方法分析1996年1月至1999年8月共78例ICP孕妇,结果提示病情越重皮肤瘙痒时间出现越早;血清TBA值与肝功能ALT、AST值呈正相关关系;血清TBA值明显升高者,羊水污染率明显增多;妊娠结局,78例ICP中发生早产13%,难产54%,胎儿窘迫44%,分别比同期孕妇的各项发生率显著增高.结论测定血清TBA对ICP有确切的诊断价值,是早期诊断ICP的最佳方法,它能真实地反映和预测其发生妊娠不良结局的可能性,做到早发现、早诊断、早治疗,病情未能控制的需适时终止妊娠可降低围产儿病死率.     

妊娠期肝内胆汁淤积症肝功能指标与胎盘形态测量的关系分析

目的探讨妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy，ICP）患者血清甘胆酸（CG）、胆红素（TBIL、DBIL）及转氨酶（AST、ALT）与胎盘绒毛间隙面密度及合体结节面密度的相关性。方法选择ICP晚期妊娠60例，正常晚期妊娠25例，测定母体血清CG、TBIL、DBIL、AST、ALT值，运用体视学方法测量胎盘绒毛间隙面密度和合体结节面密度。结果ICP患者血清CG、TBIL、DBIL、AST、ALT值明显升高，其胎盘绒毛间隙的面密度减小，合体结节的面密度增大。血清CG、TBIL、DBIL、AST、ALT值与胎盘绒毛间隙面密度呈负相关，与合体结节面密度呈正相关，且有非常显著性差异（P〈0．01）。结论ICP患者母体血清CG、DBIL、ALT、TBIL、AST值升高与胎盘形态学变化有关。     

妊娠肝内胆汁淤积症患者胎儿缺氧的影响因素

目的　探讨妊娠肝内胆汁淤积症 (ICP)患者胎儿缺氧机理及其相关因素。方法　分别测定ICP患者 (30例 ,ICP组 )及正常妊娠妇女 (30例 ,对照组 )新生儿脐动脉血胆汁酸总量 (TBA)、次黄嘌呤 (HX)、内皮素 (ET)及有核红细胞 (NRBC)计数。结果　 (1)ICP组缺氧者 (10例 )脐血HX水平为(18.6 8± 15 .73) μmol/L ,明显高于ICP组无缺氧者 (2 0例 ) [(6 .87± 2 .82 ) μmol/L ]及对照组 [(6 .81±2 .83) μmol/L](P <0 .0 1) ;但NRBC[(4 .2 0± 2 .49)个 / 10 0白细胞 ,(3.40± 2 .2 6 )个 / 10 0白细胞 ,(3.5 0± 1.74)个 / 10 0白细胞 ]及ET水平 [(72 .44± 12 .2 3)ng/L ,(70 .16± 2 6 .6 1)ng/L ,(6 7.2 7± 43.5 6 )ng/L],各组相似 (P >0 .0 5 )。 (2 )ICP组缺氧者脐血TBA为 (2 3.77± 11.82 ) μmol/L ,明显高于ICP组无缺氧者 (14.86± 5 .46 ) μmol/L ,ICP组无缺氧者脐血TBA又高于对照组 [(9.2 8± 4.39) μmol/L](P <0 .0 1) ;且ICP组脐血TBA与HX水平呈正相关 (r=0 .6 89,P <0 .0 1) ;ICP组羊水胎粪污染率明显高于对照组 (5 3.3% ,13.3% ;P <0 .0 1) ,ICP组羊水胎粪污染者脐血TBA[(2 1.44± 9.92 ) μmol/L],明显高于羊水清亮者 [(13.6 9± 5 .74) μmol/L],差异有显著性 (P <0 .0 5 )。 结论　ICP时 ,     

妊娠期肝内胆汁淤积症患者血清中白细胞介素18、12及肿瘤坏死因子α的水平变化及其临床意义

目的 探讨白细胞介素(IL)18、IL-12及肿瘤坏死因子α(TNF-α)在妊娠期肝内胆汁淤积症(ICP)患者肝功能异常中的作用.方法 选择2010年4-9月在重庆医科大学附属第一医院就诊的62例ICP患者为ICP组,其中重度患者32例,轻度患者30例;同期就诊的30例健康孕妇为对照组,另选同期在重庆医科大学附属第一医院感染科住院的30例乙型肝炎妇女为肝炎组.采用ELISA 法测定IL-18、IL-12及TNF-α水平.检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平.同时观察ICP组及对照组的围产儿结局.结果 (1)肝炎组血清中IL-18、IL-12、TNF-α水平分别为(256±51)、(122±96)、(207±3)ng/L,ALT、AST水平分别为(363±174)、(359±237)U/L;ICP组IL-18、IL-12、TNF-α水平分别为(72±32)、(42±28)、(48±14)ng/L,ALT、AST水平分别为(201±128)、(132±87)U/L;对照组IL-18、IL-12、TNF-α水平分别为(43±13)、(10±3)、(33±9)ng/L,ALT、AST水平分别为(13±4)、(15±3)U/L.肝炎组血清中IL-18、IL-12、TNF-α及ALT、AST 水平显著高于ICP组和对照组,差异均有统计学意义(P＜0.05);ICP组也显著高于对照组,差异均有统计学意义(P＜0.05).(2)ICP组重度患者血清中IL-18、IL-12、TNF-α水平分别为(81±32)、(50±25)、(50±14)ng/L,ALT、AST水平分别为(269±111)、(181±73)U/L;轻度患者IL-18、IL-12、TNF-α水平分别为(48±18)、(17±4)、(40±10)ng/L,ALT、AST水平分别为(87±46)、(50±21)U/L,ICP组重度患者血清中IL-18、IL-12、TNF-α及AST、ALT水平显著高于轻度患者和对照组,差异均有统计学意义(P＜0.05);轻度患者血清中AST和ALT水平显著高于对照组,差异有统计学意义(P＜0.05).(3)ICP组重度患者的早产儿发生率(50%,16/32)及羊水胎粪污染率(31%,10/32)显著高于轻度患者[分别为7%(2/30)及3%(1/30)]和对照组[分别为3%(1/30)及3%(1/30)],差异均有统计学意义(P＜0.05);重度患者新生儿1分钟Apgar评分≤7分的例数(2例)与轻度患者(1例)和对照组(1例)比较,差异无统计学意义(P＞0.05).结论 IL-18、IL-12和TNF-α可能参与ICP患者肝细胞损害的过程,其水平升高有助于临床诊断ICP患者的肝细胞损害.

Abstract：

Objective To investigate the effect of Interleukin(IL)-18,IL-12 and tumor necrosis factor-α(TNF-α)in hepatic injury in intrahepatic cholestasis of pregnancy(ICP).Methods Sixty-two cases of ICP patients(ICP group),30 cases of normal pregnant women(control group)and 30 cases of hepatitis B(HBV) women (hepatitis group) were recruited. Serum IL-18, IL-12 and TNF-α were examined by ELISA. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined by automatic biochemical analysis instrument. Results ( 1 ) In hepatitis group, serum concentrations of IL-18,IL-12 and TNF-α were (256±51 ) ng/L, ( 122±96) ng/L and (207±3) ng/L; serum levels of ALT and AST were(363±174) U/L and (359 ±237) U/L, respectively. In ICP group, serum concentrations of IL18, IL-12 and TNF-α were (72±32) ng/L, (42 ±28) ng/L and (48±14) ng/L; serum levels of ALT and AST were (201 ±128) U/L and ( 132±87) U/L, respectively. While in control group, serum concentrations of IL-18, IL-12 and TNF-α were (43 ± 13) ng/L, ( 10±3) ng/L and (33±9) ng/L; serum levels of ALT and AST were (13 ~ 4) U/L and (15 ± 3) U/L, respectively. Serum IL-18, IL-12, TNF-α, ALT and AST levels in hepatitis group were significantly higher than those in ICP group and control group ( P ＜0. 05 ).Serum IL-18, IL-12, TNF-α, ALT and AST levels in ICP group were significantly higher than those in control group(P ＜ 0. 05 ). (2) In severe ICP subgroup, serum concentrations of IL-18, IL-12 and TNF-α were (81 ±32) ng/L, (50 ±25) ng/L and(50 ± 14) ng/L; serum levels of ALT and AST were (269 ± 111 ) U/L and (181±73) U/L In mild ICP subgroup, serum concentrations of IL-18, IL-12 and TNF-α were (48 ±18 ) ng/L, (17 ± 4 ) ng/L and (40 ± 10 ) ng/L; serum levels of ALT and AST were (87±46) U/L and (50 ±21 ) U/L, respectively. Serum IL-18, IL-12, TNF-α, ALT and AST levels in severe ICP subgroup were significantly higher than those in mild ICP subgroup and control group (P ＜ 0. 05). And serum ALT and AST levels in mild ICP subgroup were significantly higher than those in control group(P ＜0. 05). (3) There were 16 cases with preterm birth (50%, 16/32 ) and 10 cases with meconium-stained amniotic fluid( 31%, 10/32 ) in severe ICP subgroup, significantly higher than those in mild ICP subgroup ( P＜ 0. 05 ), which contained 2 preterm births ( 7%, 2/30) and 1 meconium-stained amniotic fluid (3%, 1/30). While in control group, the numbers were 1(3%, 1/30)and 1(3%, 1/30),respectively. As for the cases of neonates whose 1 minute Apgar score were not more than 7, there were 2 cases, 1 case and 1 case in severe ICP subgroup, mild ICP subgroup and control group, respectively,which showed no significant difference(P＞ 0. 05). Conclusion Serum IL-18, IL-12 and TNF-α may be involved in the process of hepatic injury of ICP.     

妊娠期肝内胆汁淤积症对胎鼠肺脏形态的影响

目的 探讨孕鼠发生肝内胆汁淤积症(ICP)时对胎鼠肺脏形态学的影响.方法 将妊娠15 d的20只SD孕鼠随机分为实验组和对照组,每组10只.实验组孕鼠皮下注射17α-乙炔雌二醇和孕酮,连续5 d,成功建立ICP大鼠模型;对照组孕鼠皮下注射精制植物油,连续5 d.分别测定两组孕鼠模型建立前、后血清中丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆汁酸(TBA)的水平.于妊娠第21天处死孕鼠,取出孕鼠肝脏组织;处死孕鼠后立即行剖宫取胎术,对取出的胎鼠肺组织和孕鼠肝脏组织进行光镜和电镜的病理学检查.结果 (1)生化指标:模型建立前,实验组孕鼠血中ALT、AST及TBA水平分别为(55±15)U/L、(146±16)U/L及(13±4)μmol/L;对照组分别为(49±12)U/L、(145±20)U/L及(14±4)μmol/L,两组比较,差异无统计学意义(P>0.05).模型建立后(于妊娠第21天断颈处死孕鼠),实验组孕鼠血中ALT、AST及TBA水平分别为(94±12)U/L、(245±26)U/L及(44±16)μmol/L;对照组分别为(59±17)U/L、(163±27)U/L及(17±3)μmol/L,两组比较,差异有统计学意义(P<0.05).(2)孕鼠肝脏病理学检查:大体所见,实验组孕鼠肝脏边缘钝厚,色泽灰暗;对照组孕鼠肝脏边缘锐利,色泽红润.光镜下所见,实验组孕鼠中有部分肝细胞肿胀变性,胞质疏松化,肝血窦受压变窄,部分胆管扩张,偶见肝细胞坏死;对照组孕鼠则肝细胞形态及肝小叶结构均正常.(3)胎鼠肺脏组织学检查:实验组胎鼠肺脏色泽灰暗,对照组胎鼠肺脏外观红润.光镜下所见,实验组胎鼠肺组织已发育成熟,但肺间质毛细血管明显扩张、充血,大部分肺泡间隔增宽,肺泡内少量炎性渗出物,灶状肺泡内出血.电镜下所见,肺泡Ⅱ型细胞微绒毛减少,线粒体空泡变性,部分细胞质崩解,板层小体排空增多;对照组为正常肺组织病理表现,肺组织结构清晰,肺泡壁薄,肺泡腔内偶见巨噬细胞,未见炎性细胞浸润.结论 联合应用雌、孕激素能够有效地建立ICP孕鼠模型,且ICP孕鼠的高胆汁酸血症对胎鼠肺组织有明显的毒性损伤作用,导致肺组织发生严重的病理改变.     

熊去氧胆酸联合低分子肝素钙注射液与丁二磺酸腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症的临床研究

目的:观察熊去氧胆酸联合低分子肝素钙注射液与丁二磺酸腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)患者的临床疗效,分析患者血清胆汁酸(TBA)、谷丙转氨酶(ALT)和谷草转氨酶(AST)水平的变化及妊娠情况。方法:将收治的135例ICP患者按照治疗方法不同分为A、B、C组,各45例,3组均行常规检查。A组口服熊去氧胆酸片;B组口服熊去氧胆酸片基础上注射丁二磺酸腺苷蛋氨酸治疗;C组在B组治疗基础上联合低分子肝素钙治疗。对比3组临床疗效和妊娠情况,检测所有受试者治疗前后外周血TBA、ALT和AST水平。结果:治疗后,C组临床有效率(93.33%)高于A、B组(P0.05)。治疗前,3组患者瘙痒评分比较差异无统计学意义(P0.05);治疗后,3组瘙痒评分较组内治疗前均降低(P0.05),且治疗后C组低于A和B组(P0.05),B组低于A组(P0.05)。治疗前,3组TBA、ALT和AST水平差异无统计学意义(P0.05);治疗后,3组TBA、ALT和AST水平较组内治疗前均降低(P0.05),且治疗后C组低于A和B组,B组低于A组(P0.05)。治疗后,C组患者剖宫产、早产、胎儿窘迫和羊水污染发生率均低于A组和B组,且总不良反应发生率明显低于A组和B组(P0.05)。结论:熊去氧胆酸联合低分子肝素钙注射液与丁二磺酸腺苷蛋氨酸治疗ICP患者的临床疗效显著,能更有效缓解患者的瘙痒程度,降低血清TBA、ALT和AST水平,保护肝脏,减少胎儿窘迫和羊水污染等情况的发生,具有较高临床价值,可作为ICP的治疗方案进一步推广应用。     

Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy with dichorionic diamniotic twin pregnancies

Objective: The aim of our study was to investigate the predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with dichorionic diamniotic (DCDA) twin pregnancies.

Methods: This study was a retrospective study of women diagnosed with ICP and DCDA twin pregnancies in Chengdu’s women and children’s central hospital. These patients were subdivided into mild and severe ICP groups according to total bile acid (TBA) level. The clinical characteristics and perinatal outcomes were collected and compared between the two groups. Logistic regression analysis was developed to evaluate predictors of adverse perinatal outcomes.

Results: About 134 cases were included in the study. Eighty-four cases were in the mild ICP group, and the other 50 cases were in the severe ICP group. Level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and direct bilirubin (DBIL) in the severe ICP group were significant higher than those in the mild ICP group. The rate of delivery before 34 gestational weeks, meconium-stained amniotic fluid, and composite adverse neonatal outcome were higher in the severe ICP group than those in the mild ICP group. After adjusting for confounders, ICP onset gestational age (GA)?<30 weeks and AST >200U/l were associated with GA at delivery <34 weeks. ALP >400U/l was an independent risk factor of meconium-stained amniotic fluid. ICP onset GA <30 weeks was an independent risk factor of composite adverse neonatal outcome.

Conclusion: ICP onset GA <30 weeks, TBA >40 µmol/l, AST >200U/l, and ALP >400U/l were associated with composite adverse perinatal outcomes in ICP with DCDA twin pregnancies. For those patients with these characteristics, fetal surveillance and treatment should be enhanced.     

Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy

Our objective was to examine whether delivery at 37 weeks of gestation alters adverse pregnancy outcomes in Latina patients with intrahepatic cholestasis of pregnancy (ICP). We conducted a retrospective chart review of Latina patients who delivered at our institution coded with ICP between 2000 and 2007. During this time period it was our practice to offer delivery to patients with ICP at 37 weeks of gestation. Subjects were classified into three groups according to total bile acid (TBA) concentration: < 20 micromol/L (mild ICP), > or = 20 micromol/L and < 40 micromol/L (moderate ICP), and > or = 40 micromol/L (severe ICP). Meconium passage was observed in no births in patients with mild IC, but was found in 18% of deliveries with moderate/severe ICP. The risk of meconium passage increased linearly, with a 19.7% increased risk for each 10 mumol/L increase in TBA concentration ( P = 0.001). There was no association with higher TBA concentration and other adverse outcomes. There was no difference in adverse outcomes between moderate and severe ICP. We concluded that in our Latina population with ICP, an association existed between meconium passage and moderate/severe ICP. Delivering at 37 weeks was associated with a low risk of adverse outcomes due to ICP among all patients, including those with higher TBA concentrations.     

SAMe对雌激素诱导的肝内胆汁淤积症孕鼠的胎盘多药耐药相关蛋白-谷胱甘肽共转运体系的影响

目的:探讨S-腺苷蛋氨酸(SAMe)对雌激素诱导的肝内胆汁淤积症(ICP)孕鼠的胎盘多药耐药相关蛋白(MRP)-谷胱甘肽(GSH)共转运体系的影响。方法:将妊娠第13天的大鼠随机分成对照组(孕15～19天腹腔注射生理盐水)、EE(孕15～19天皮下注射17-α-乙炔雌二醇溶液)组、EE+SAMe组(孕15～19天皮下注射17-α-乙炔雌二醇溶液,孕17～19天腹腔注射SAMe溶液)。17-α-乙炔雌二醇诱导孕鼠发生肝内胆汁淤积,建立ICP模型,测定3组血清总胆酸(TBA)、甘胆酸(CG)、血清丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST);ELISA检测GSH,逆转录实时荧光定量PCR和免疫组化法检测MRP1、MRP2、MRP5的表达。结果:EE组的TBA、CG、ALT、AST水平显著增高,胚胎存活率显著降低(P0.001);经SAMe治疗,TBA、CG、ALT、AST水平显著下降,增加了胚胎存活率(P0.01)。EE组胎盘的MRP1 mRNA和蛋白表达显著上调(P0.05),而胎盘MRP2、MRP5 mRNA和蛋白的表达显著下调(P0.01),GSH显著下降(P0.001);经SAMe治疗,胎盘MRP1 mRNA和蛋白表达显著下调(P0.05),胎盘MRP2、MRP5 mRNA和蛋白的表达显著上调(P0.05),GSH显著上升。结论:胎盘存在MRP-GSH共转运体系;SAMe可通过调节胎盘MRP-GSH共转运体系影响胆汁酸的转运,从而治疗大鼠妊娠期ICP。     

S-腺苷甲硫氨酸联合还原型谷胱甘肽治疗妊娠期肝内胆汁淤积症

【摘 要】 目的：探讨S-腺苷甲硫氨酸（S-adenosylmethionine,SAM）联合还原型谷胱甘肽治疗妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）的临床效果。方法：选取本院2012年1月-2015年6月收治的117例ICP患者采用SPSS 16.0软件生成随机数字表后分为联合组58例和对照组59例,2组患者均采用SAM+常规治疗,联合组加用还原型谷胱甘肽治疗,2组患者的疗程均为4周,对比2组的治疗效果。结果：治疗前联合组和对照组的血总胆汁酸（TBA）、谷丙转氨酶（ALT）、谷草转氨酶（AST）水平及瘙痒程度评分差异无统计学意义（P＞0.05）;治疗后2组患者的血TBA、ALT、AST水平及瘙痒程度评分均较本组治疗前显著降低（P＜0.05）;治疗后,联合组患者的血TBA、ALT、AST水平及瘙痒程度评分低于对照组患者,差异有统计学意义（P＜0.05）;2组分娩孕周、胎儿窘迫、Apgar评分及新生儿体质量比较,差异无统计学意义（均P＞0.05）;联合组剖宫产率显著低于对照组,差异有统计学意义（P＜0.05）。结论：还原型谷胱甘肽联合SAM治疗ICP较单用SAM具有更加显著的临床效果。     

妊娠期肝内胆汁淤积症患者血清及新生儿脐血中可溶性细胞间粘附分子-1的检测及临床意义

目的 :检测妊娠期肝内胆汁淤积症 (ICP)患者血清及新生儿脐血中可溶性细胞间粘附分子 - 1(SICAM - 1)及其临床意义。方法 :采用酶联免疫吸附法 (ELISA)检测各项指标。结果 :(1)ICP患者血清、新生儿脐血中SICAM - 1的浓度明显高于正常孕妇组 (P<0 .0 1) ,随着ICP程度的增加 ,SICAM - 1的浓度逐渐增高 (P <0 .0 5 ) ;两组孕妇产后 1周母血中SICAM - 1逐渐降至正常 (P >0 .0 5 ) ;(2 )ICP患者血清中SICAM - 1的升高与胆汁酸 (BA)、ALT、AST呈正相关 (P <0 .0 0 1,P <0 .0 0 5 )。结论 :ICP患者血清、新生儿脐血中SICAM - 1含量的升高在ICP的发病中可能有一定的作用     

妊娠期肝内胆汁淤积症胎儿胆汁酸水平与肺表面活性物质的相关性研究

目的 探讨妊娠期肝内胆汁淤积症(ICP)胎儿总胆汁酸水平与胎儿肺表面活性物质(PS)的关系.方法 选择2008年4月至2010年2月在中南大学湘雅二医院住院行剖宫产分娩的ICP孕妇55例(ICP组),记录ICP组孕妇的新生儿出生至产后7 d的一般情况,凡符合胎儿窘迫、新生儿窒息、新生儿呼吸窘迫综合征其中1项者为病理围产儿,无上述情况为正常围产儿.另选同期健康孕妇23例为对照组.采用循环酶法测定两组孕妇血、脐血及羊水中总胆汁酸水平;ELISA法测定两组胎儿脐血肺表面活性蛋白A(SP-A)水平;高效液相色谱法测定两组羊水中磷脂酰胆碱(PC)、磷脂酰肌醇(PI)、溶血卵磷脂(LPC)、神经鞘磷脂(SM)的含量.结果 (1)ICP组孕妇血、脐血及羊水中总胆汁酸水平分别为(30.1±7.9)、(9.3±3.3)及(4.4 ±1.5)mmol/L,明显高于对照组的(4.8±2.2)、(4.9±0.9)及(1.4±1.1)mmol/L,两组分别比较,差异均有统计学意义(P＜0.05).(2)ICP 组胎儿脐血SP-A水平为(29.5±6.4)μg/L,明显高于对照组的(22.6±7.4)μg/L,两组比较,差异均有统计学意义(P＜0.05).(3)ICP组中病理围产儿20例,健康围产儿35例,病理围产儿脐血总胆汁酸及SP-A水平分别为(10.9±2.2)mmol/L及(37.0±5.9)μg/L,健康围产儿分别为(8.0±2.8)mmol/L及(26.7±4.8)μg/L,两者比较,差异有统计学意义(P＜0.05).(4)脐血总胆汁酸水平分别与孕妇血、羊水总胆汁酸水平呈正相关(r1=0.706,r2=0.763,P＜0.05);脐血SP-A水平与脐血总胆汁酸水平呈正相关(r3=0.494,P＜0.05).(5)ICP组羊水中PC及PI的含量分别为(65.4±7.2)及(3.8±0.6)mg/L,均明显低于对照组的(69.7±3.7)及(4.3±0.7)mg/L,两组比较,差异有统计学意义(P＜0.05);ICP组羊水LPC的含量为(4.8±0.9)mg/L,明显高于对照组的(4.2±0.6)mg/L,两组比较,差异有统计学意义(P＜0.05);ICP组羊水SM的含量为(3.5±0.8)mg/L,与对照组的(4.0±0.5)mg/L比较,差异无统计学意义(P＞0.05).(6)ICP组羊水PC/LPC比值(14.2±3.2)明显低于对照组(16.9±2.5),差异有统计学意义(P＜0.05).(7)脐血总胆汁酸水平与羊水PC、PI的含量均呈负相关(r1=-0.561,r2=-0.407,P＜0.05);与LPC含量无相关性(r3=0.260,P＞0.05).结论 ICP孕妇的胎儿脐血及羊水中总胆汁酸水平均明显高于健康孕妇,其胎儿PS的改变与胎儿体内高总胆汁酸水平有关.

Abstract：

Objective To explore the relationship between total bile acid(TBA)concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy(ICP).Methods Fifry five patients with ICP(ICP group)who received cesarean section from April 2008 to February 2010 in Second Xiangya Hospital,Central South University,were recruited.The general conditions of the neonates within 7 days after birth in ICP group were recorded.Those with fetal distress,neonatal asphyxia,or neonatal respiratory distress syndrome were referred as pathological neonates, others were referred as normal neonates. Over the same period, 23 healthy gravidas were recruited as control group. Enzymatic method was used to detect the TBA concentrations in maternal blood, cord blood and amniotic fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration in cord blood. High performance liquid chromatography system was used to detect the concentrations of phesphatidylcholine (PC),phosphatidylinositol (PI),lysophosphatidylcholine ( LPC), and sphingomyelin(SM) in amniotic fluid. Results ( 1 ) The concentrations of TBA in maternal blood, cord blood and amniotic fluid were ( 30. 1 ± 7.9 ), (9. 3± 3. 3 ) and (4. 4 ± 1.5 ) mmol/L in ICP group, (4. 8 ± 2. 2), (4. 9 ± 0. 9) and ( 1.4 v 1.1 ) mmol/L in control group, respectively. The differences between the two groups were significant ( P ＜ 0. 05 ). ( 2 ) The SP-A concentration in cord blood in ICP group was ( 29. 5 ± 6. 4 ) μg/L, significantly higher than that in control group, which was ( 22. 6 ± 7. 4 )μg/L ( P＜ 0. 05 ). ( 3 ) There were 20 pathological neonates and 35 normal neonates in ICP group. In pathological neonates, the concentrations of TBA and SP-A in cord blood were (10.9 ± 2.2) mmol/L,(37.0 ± 5.9 ) μg/L, respectively; and were ( 8.0 ± 2. 8 ) mmol/L, ( 26. 7 ± 4. 8 ) μg/L in normal neonates. The differences were significant (P＜ 0. 05 ). (4) There was a positive correlation between TBA concentration in cord blood and in maternal blood ( r1 = 0. 706, P＜0. 05 ). The TBA concentration in cord blood was positively correlated with SP-A concentration as well ( r3 = 0. 494,P ＜ 0. 05 ). (5) The PC and PI concentrations in amniotic fluid were (65.4 ± 7.2) mg/L and ( 3. 8 ± 0. 6 ) mg/L in ICP group, ( 69. 7 ±3.7) mg/L and (4. 3 ± 0. 7 ) mg/L in control group, respectively. The differences were significant (P ＜0. 05 ). The concentration of LPC in amniotic fluid in ICP group was (4. 8 ±0. 9) mg/L, significantly higher than that in control group (P＜0. 05), which was (4. 2 ±0. 6) mg/L. The concentration of SM in amniotic fluid was (3.5±0. 8) mg/L in ICP group, (4. 0 ± 0. 5 ) mg/L in control group, with no significant difference ( P＞0. 05 ). (6) The ratio of PC/LPC in ICP group ( 14. 2± 3. 2 ) was significantly lower than that in control group ( 16. 9 ± 2. 5 ) ( P＜ 0. 05 ). ( 7 ) The TBA concentration in cord blood was negatively correlated with PC and PI concentrations (r1 = -0. 561, r2 = -0. 407, P ＜ 0. 05 ), and had no correlation with LPC concentration (r3 = 0. 260, P＞ 0. 05). Conclusions ( 1 ) The fetal TBA concentrations in both cord blood and amniotic fluid of patients with ICP was higher than those of healthy gravidas, they were also positively correlated with maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary surfactant and this change was associated with TBA concentrations in both cord blood and amniotic fluid.     

Prediction of preeclampsia: liver function tests during the first 20 gestational weeks

Objective: To examine whether plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the first 20 weeks of pregnancy can predict preeclampsia in the second half of pregnancy. Methods: The study population included 150,10 registered births. Receiver operating characteristic (ROC) curve analysis was used to describe the relationship between different values of AST and ALT during the first 20 weeks of pregnancy in the prediction of preeclampsia. Results: Using ROC curve analyses, elevated ALT levels were significantly associated with both mild preeclampsia (p < 0.001) and severe preeclampsia (p = 0.032). However, an ALT level of 50 IU/L had a sensitivity of only 3.3% (despite a specificity of 97%) in the prediction of severe preeclampsia. While no significant association was noted between AST levels and mild preeclampsia (p = 0.669), elevated levels of AST during this period were significantly associated with severe preeclampsia (p = 0.027). However, AST of 50I U/L had a sensitivity of only 2.0% (despite a specificity of 98%) in the prediction of severe preeclampsia. Conclusions: Higher levels of the liver enzymes AST and ALT during the first 20 weeks of pregnancy are associated with higher risk for the development of severe preeclampsia in the second half of the pregnancy. Nevertheless, there is no clinical cutoff value that can be practically used for the prediction of preeclampsia.     

丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者免疫功能及疗效的影响

目的：探讨丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症（ＩＣＰ）患者免疫功能及疗效的影响。方法：选取2013年9月—2015年9月住院的ICP患者78例,将所有研究对象分为观察组与对照组,各39例,对照组采用丁二磺酸腺苷蛋氨酸治疗,观察组采用丁二磺酸腺苷蛋氨酸联用地塞米松联合治疗。比较2组治疗前后血清总胆汁酸（TBA）、总胆红素（TBIL）、直接胆红素（DBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、白细胞介素12（IL-12）及肿瘤坏死因子α（TNF-α）水平,比较2组产后胎盘组织中TNF-α的表达水平及治疗效果。结果：观察组的治疗效果优于对照组,妊娠结局与围生儿状况同样优于对照组（P＜0.05）。2组患者治疗后TBA、TBIL、ALT、AST及IL-12水平均明显下降（P＜0.05）,且观察组较对照组下降更明显（P＜0.05）。观察组DBIL、TNF-α及产后胎盘TNF-α水平均低于对照组,观察组各指标治疗前后差值均高于对照组（P＜0.05）。结论：丁二磺酸腺苷蛋氨酸联合地塞米松治疗ICP,在缓解患者临床体征、降低血胆汁酸及改善肝功能等方面有显著的临床效果,并可改善患者的免疫功能状态、妊娠结局及围生儿状况。