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母胎混合淋巴细胞培养的研究

目的　通过观察母胎间混合淋巴细胞反应 ,探讨母胎组织相容性与妊娠期肝内胆汁淤积症 (ICP)发病的关系。方法　采用淋巴细胞转化法对 2 2例ICP患者 [ICP组 ,其中 5例合并妊娠高血压综合征 (妊高征 ) ]和 2 1例正常孕妇 (对照组 )进行母胎淋巴细胞混合培养 ,计算淋巴细胞转化率 ;比较两组间淋巴细胞转化率的差异。通过检测ICP组孕妇的血清甘胆酸盐水平 ,分析淋巴细胞转化率与血清甘胆酸盐水平的相关性。结果　ICP组淋巴细胞转化率为 ( 2 4± 5 ) % ,对照组为 ( 3 6± 9) % ,两组比较 ,差异有极显著性 (P <0 0 0 1)。ICP组合并与不合并妊高征者的淋巴细胞转化率无显著性差异 (P >0 0 5 )。ICP组淋巴细胞转化率与血清甘胆酸盐水平无显著相关性 [相关系数 (r) =0 40 3 ,P>0 0 5 ]。结论　ICP患者母胎混合淋巴细胞培养反应性降低 ,提示母胎间组织相容性增高、免疫识别与反应性降低。这一变化可能与ICP的发生有关     

妊娠肝内胆汁淤积症与胎儿生长受限关系的探讨

目的 :探讨妊娠肝内胆汁淤积症 (ICP)与胎儿生长受限 (FGR)的关系。方法 :回顾性分析 6 1例ICP患者与对照组妊娠结局、新生儿体重、FGR发生率的比较及ICP新生儿体重与胆汁酸、肝功能的关系。结果 :ICP组早产、羊水粪染、Apgar评分 <7分 (1分钟 )的发生率与对照组比较差异有非常显著性 ,P <0 .0 1。ICP组新生儿平均体重为 (32 33.9±14 75 .5 )g ,FGR的发生率为 3 3% ,与正常组相比差异无显著性。多元线性回归分析 ,ICP组新生儿体重与胆汁酸、肝功能无明显线性关系。结论 :ICP与胎儿生长受限之间无明显相关性     

妊娠肝内胆汁淤积症患者体液免疫功能的变化及临床意义

目的 :探讨妊娠期肝内胆汁淤积症 (ICP)体液免疫变化的特点及其临床意义。方法 :采用速率散色比浊法和速率法检测 6 0例妊娠晚期ICP患者和 5 0例正常孕妇血清免疫球蛋白、血清补体C3 、C4和胆汁酸水平 ,并观察其与母婴并发症和妊娠结局的关系。结果 :①ICP组IgG水平为 8.2 9± 2 .0 1g/L ,显著低于正常妊娠组 10 .2± 1.97g/L(P <0 .0 5 ) ,IgM水平为 2 .72± 0 .93g/L ,明显高于正常妊娠组 1.6 2± 0 .84g/L(P <0 .0 5 ) ;②ICP患者血清IgG和IgM水平分别与体内胆汁酸浓度 (4 9.99± 36 .1) μmol/L呈负相关和正相关 ,相关系数 (r)分别为 - 0 .5 12和 0 .32 7(P <0 .0 5 ) ;③如将 95 %正常妊娠妇女体液免疫数值作为正常值范围 ,把ICP患者分为体液免疫异常组和正常组 ,则异常组羊水粪染、胎儿宫内窘迫、早产及围生儿死亡率明显增高。结论 :大部分ICP患者的部份体液免疫功能发生了改变 ,其异常程度与围生期母儿结局明显相关 ,可作为监测ICP病情程度的指标     

妊娠肝内胆汁淤积症妇女血清一氧化氮水平的研究

目的探讨一氧化氮（ＮＯ）与妊娠肝内胆汁淤积症（ＩＣＰ）病理生理变化之间的关系。方法采用Ｇｒｅｉｓｓ法测定４９例ＩＣＰ妊娠妇女（ＩＣＰ组）外周血中ＮＯ的含量,同期住院的正常晚期妊娠妇女２６例（正常妊娠组）作为对照。结果ＩＣＰ组妊娠妇女血清ＮＯ含量较正常晚期妊娠组明显降低（Ｐ＜０．０１）;ＩＣＰ组妊娠妇女血清ＮＯ水平与瘙痒症状持续时间、血清胆红素和转氨酶值的高低有关,而与血清甘胆酸（ＣＧ）无相关性。ＩＣＰ组平均孕龄较正常妊娠组缩短,平均新生儿体重显著低于正常妊娠组。结论ＮＯ参与了ＩＣＰ的病理生理变化过程,与ＩＣＰ妊娠妇女并发的胎儿宫内发育迟缓（ＩＵ－ＧＲ）、早产、胎儿宫内窘迫等有一定关系     

妊娠期肝内胆汁淤积症128例临床分析

因妊娠期肝内胆汁淤积症（ｉｎｔｒɑｈｅｐɑｔｉｃｃｈｏｌｅｓｔɑｓｉｓｏｆｐｒｅｇｎɑｎｃｙ,ＩＣＰ）可引起早产,胎儿宫内窘迫（ＦＩＵＤ）,围产儿死亡（ｐｅｒｉｎɑｔɑｌｉｎｆɑｎｔｄｅɑｔｈ）及产后出血,受到产科医生的重视。现对１９９１年１月１日至...     

CD4+CDhigh25调节性T淋巴细胞在妊娠肝内胆汁淤积症发病中的作用

目的 探讨妊娠肝内胆汁淤积症(ICP)患者外周血与蜕膜组织CD4+CD25+凋节性T淋巴细胞(Treg细胞)及CD4+CD25hJigh细胞在ICP发病中的作用.方法 采用流式细胞仪检测30例ICP患者(ICP组,其中轻度15例,重度15例)及28例正常晚期妊娠妇女(对照组)外周血和蜕膜组织CD4+CD25+Treg细胞及CD4+CD25hJigh细胞占CD+T淋巴细胞的百分率,分析其与ICP发病的关系.结果 ICP组外周血CD4+CD25+Treg细胞百分率为(7.96±1.32)%,CD4+CD25high细胞了百分率为(0.78±0.22)%,均低于对照组[(17.05±2.86)%、(1.71±0.69)%],分别比较,差异均有统计学意义(P<0.01);ICP组蜕膜组织CD4+CD25+Treg细胞百分率为(17.18±2.27)%,CD+4CD25highTreg细胞百分率为(2.25±0.89)%,也均低于对照组[(32.01±3.88)%、(8.30±1.13)%],分别比较,差异也均有统计学意义(P<0.01).ICP组及对照组蜕膜组织中CD4+CD25+Treg细胞及CD4+CD25highTreg细胞百分率均高于外周血,差异均有统计学意义(P<0.01).ICP组轻度及重度患者外周血CD4+CD25+Treg细胞百分率分别为(8.74±0.96)%、(7.17±1.17)%,CD4+CD25hiithTreg细胞百分率分别为(0.89 ±0.20)%、(0.68±0.19)%,而蜕膜组织CD4+CD25+Treg细胞百分率分别为(18.43 ±1.90)%、(15.94±1.95)%,CD4+CD25highTreg细胞百分率分别为(2.62±0.72)%、(1.87±0.90)%,ICP组外周血及蜕膜组织CD4+CD25high胞及CD4+CD25+Treg细胞百分率随着病情的加重呈下降趋势,分别比较,差异均有统计学意义(P<0.05).结论 CD4+CD25+Treg细胞及CD4+CD25+highTreg细胞可能参与ICP的发病过程,并与病情的严重程度密切相关.     

妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症徐先明综述庄依亮审校（上海医科大学妇产科医院）妊娠期肝内胆汁淤积症（Ｉｎｔｒａｈｅｐａｔｉｃｃｈｏｌｅｓｔａｓｉｓｏｆｐｒｅｇｎａｎｃｙ，ＩＣＰ）易引起早产和胎儿窘迫、死胎、死产，近年来受到产科医生的重视，被列为高危妊娠之一，目前...     

妊娠肝内胆汁淤积症1241例发病特点分析

目的探讨妊娠肝内胆汁淤积症(ICP)的发病特点。方法采用回顾性分析的方法,对我院1991年1月至2000年12月收治的1241例ICP患者的临床资料进行回顾性系统分析。结果1241例ICP患者中,多胎妊娠44例(3．5％),合并妊娠高血压综合征(妊高征)。101例(8．1％);。126例经产妇中,38例(30．2％)为ICP复发;有发病时间记录的1230例患者的平均发病孕周为32．6周,孕晚期发病有1100例(88．6％);1201例(96．8％)以皮肤瘙痒为首发症状,也有以黄疸(8例,占0．6％)、肝功能异常(28例,占2．3％)等为起始表现者;生化指标中主要以血清总胆汁酸(TBA)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)升高为主,但大多为轻、中度升高;也有患者TBA、ALT或AST正常(分别占17．7％、15．6％、17．1％),少数患者(35例,3．2％)白蛋白／球蛋白比值倒置。结论 (1)ICP具有复发性,多胎妊娠孕妇更易发病,瘙痒常是ICP显著而且首发的症状,TBA和肝脏转氨酶升高有助于该病的诊断。(2)少数患者发病时临床表现及实验室检查结果均不典型,对此要引起警惕。     

双胎妊娠合并妊娠肝内胆汁淤积症24例报告

双胎妊娠合并妊娠肝内胆汁淤积症２４例报告陶敏芳戴钟英妊娠肝内胆汁淤积症（ＩＣＰ）常发生于妊娠中、晚期，易造成早产、胎儿窘迫及胎死宫内等。而双胎也属高危妊娠，两者并发对母、胎的危害更大。我院于１９８７年报道双胎ＩＣＰ的发生率升高［１］。现将双胎妊娠与Ｉ...     

妊娠期肝内胆汁淤积症发生死胎的临床因素分析

目的 探讨妊娠期肝内胆汁淤积症(ICP)孕妇发生胎儿死亡的临床特点、实验室指标及胎儿监护手段.方法 对1999年1月至2010年12月浙江大学医学院附属妇产科医院收治的发生死胎的21例ICP孕妇的临床资料进行回顾性分析.结果 (1)21例ICP孕妇的平均年龄(30.2±4.6)岁,其中＞35岁者4例;经产妇6例,1例2年前因ICP发生死胎而引产1次;20例单胎妊娠,1例双胎妊娠.(2)21例ICP孕妇的死胎均发生在孕晚期,胎儿死亡的孕周为29～41周,平均(33.8±4.2)周.12例发生在孕29～37周,9例发生在孕37周后.9例为门诊B超检查时确诊胎死宫内;9例因诊断ICP入院治疗期间发生胎心消失;2例临产后胎心消失;1例胎心监护提示V型减速,拟行急诊刮宫产术于麻醉期间胎心消失.在所有ICP孕妇中围产儿死亡率为0.148%(21/14 184).(3)21例ICP孕妇均有皮肤瘙痒,其中11例有全身皮肤瘙痒.10例在发生死胎前自觉胎动减少或消失.21例ICP孕妇血清甘胆酸水平均升高,其中21.49～64.48 μmol/L 11例,t≥64.48 μmol/L 10例.血清总胆汁酸水平升高16例(另5例未检查),最高达270μmoL/L.血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高14例,总胆红素＞21μmol/L 7例,直接胆红素升高12例.21例ICP孕妇中,重度15例,轻度6例.(4)9例孕妇门诊即确诊宫内死胎未做胎心监护,其余12例住院检查结果 为:胎心监护结果 可疑2例,无应激试验(NST)提示胎心轻度V型减速1例,B超提示脐动脉舒张期血流缺如3例,胎儿生物物理指标评分低值1例.(5)21例ICP孕妇均经阴道分娩.6例为自然宫缩娩出死胎,其余15例予米非司酮配合依沙吖啶羊膜腔注射或缩宫素引产,14例在48 h内成功娩出死胎,仅1例追加地诺前列酮栓后引产成功.所有死胎外观无异常,脐带长度均在正常范围,有4例脐带绕颈或绕体.胎盘胎膜外观无异常,18例羊水Ⅲ度胎粪污染,2例合并羊水过少.10例行死胎及胎盘病理检查,其中1例合并多发畸形,其余死胎病理检查未见明显异常,10例胎盘病理检查均有绒毛膜周围或底蜕膜、大血管周围的纤维蛋白沉积,同时伴有钙化、退行性变、红色梗死及局灶性合体细胞结节增多.结论 ICP孕妇发生死胎的孕周常在孕晚期,时间常在正常宫缩后,ICP重度可能是发生死胎的关键因素;尚无有效的胎儿监护指标可预测死胎的发生.因此,应综合评估病情,加强胎儿监护,适时终止妊娠.

Abstract：

Objective To investigate the clinical features,critical laboratory parameters,and fetal monitoring methods in intrahepatic cholestasis of pregnancy(ICP).Methods A retrospective analysis of 21 cases of ICP suffered with fetal death in Women's hospital.School of Medicine.Zhejiang University from January 1999 to December 2010 were discussed.Results(1)The average age of ICP patients suffered with fetal death were(30.2±4.6)years old.Among them,4 cases were older than 35 years,six cases were multipara.oneo of them suffered stillbirth 2 year before.Twenty cases were singleton pregnancies and 1 cage was twin pregnancy.(2)All 21 cases of fetal death occurred in the third trimester,12 cases occurred before 37 weeks,9 cases after 37 weeks.Nine cases were diagnosed by ultrasound in outpatient clinics,fetal heart beat disappeared in 9 patients after admission because of ICP, two disappeared after labor, one during anesthesia before emergent surgery. Perinatal mortality rate of ICP was 0. 148% (21/14 184), and fetal death occurred from 29 to 41 weeks with an average gestational age of ( 33.8 ± 4. 2 ) weeks, ( 3 ) Puritus occurred in all 21 cases while 11 of them had pruritus all over the body. Ten pregnant women felt the fetal movement decreased or disappeared before diagnosis of fetal death. The glycocholic acid levels increased in all of the 21 cases. Among them, glycocholic acid levels in 11 cases were (21.49 -64. 48) μmol/L, while in 10 cases were ≥64. 48 μmol/L Serum bile acid levels elevated in 16 cases which had been analyzed ( the other 5 cases had not been checked ), and the highest level reached 270 μmol/L Serum alanine aminotransferase and aspartate aminotransferase were increased in 14 cases. Seven cases had their total bilirubin ＞21 μmoL/L, and 12 cases had their direct bilirubin levels significantly elevated. Among the 21 cases of ICP, 15 cases were in severe status, while the other 6 cases were mild. (4) Nine patients had no antepartum surveillance since fetal death were diagnosed before admission. The results of antepartum surveillance were as follows: 2 cases had nonreassuring nonstress test (NST), one had mild "V" type deceleration. Absence of diastolic flow in umbilical artery were found in 3 cases, and low fetal biophysical score was got in one case. ( 5 ) All 21 patients had vaginal delivery. Six of them delivered after natural contraction, and the remaining 14 cases delivered after oral intake of mifepristone and amniotic injection of ethacridine, or oxytocin induced labor within 48 hours, only one case delivered after additional dinoprostone suppositories. The appearance of fetus, placentas and membranes were normal, the lengths of umbilical cord were average. Four cases were found with cords binding the necks or the bodies. Eighteen cases had grade Ⅲ amniotic fluid with meconium-stained, and 2 cases complicated by oligohydramnios. Ten cases had their fetuses and placentas examined by pathologist. Among them, one case had multiple malformations, no more obvious pathological abnormalities were found in other fetuses. Pathologic examination showed that fibrin deposited around chorion and deciduas basalis, large vessels accompanied by calcification, degeneration,hemorrhagic infarction, and increased focal syncytial nodules could be seen in all of the ten placentas. Conclusions Fetal death in pregnant women with ICP of ten occurs after the contractions, Severe ICP may be a key factor that involved in the occurrence of fetal death. Up to now, there is no valid indicators in fetal monitoring, which can predict fetal death. Extensive assessment of the severity and careful antepartum surveillance should be achieved before timely termination of pregnancy.     

妊娠肝内胆汁淤积症分度诊断和处理的临床意义

目的　探讨妊娠肝内胆汁淤积症 (ICP)分度诊断和处理的临床意义。方法　将 1999年1月至 2 0 0 3年 5月 ,在我院产前检查并诊为ICP的 2 78例患者 ,应用我院 1999年自订的ICP分度标准 ,根据ICP患者的血清胆红素、肝转氨酶和甘胆酸水平分为轻度与重度ICP。并进行分度诊断和分度处理 ,观察其妊娠结局与分度诊断前后的围产儿死亡率。结果　 (1)轻度ICP患者为 192例 (轻度组 ) ,重度ICP患者为 86例 (重度组 )。 (2 )重度组和轻度组ICP患者终止妊娠的平均孕周分别为(35 8± 1 6 )周和 (37 7± 1 9)周 ,两组比较 ,差异有极显著性 (P <0 0 1)。 (3)重度组和轻度组ICP分度诊断后 ,期待治疗的时间为 (10± 5 )d和 (19± 6 )d ,两组比较 ,差异有极显著性 (P <0 0 0 1)。 (4)重度组ICP患者羊水粪染、新生儿窒息和新生儿转入重症监护室的发生率分别为 38 4 % (33/ 86 )、12 8% (11/ 86 )、30 2 % (2 6 / 86 ) ,明显高于轻度组的 9 4 % (18/ 192 )、4 2 % (8/ 192 )、9 4 % (18/ 192 )。(5 )采用分度诊断前围产儿死亡率为 3 9%～ 6 0 % ,分度诊断后围产儿死亡率为 0 7%～ 1 2 % ,两者比较 ,差异有极显著性 (P <0 0 1)。结论　对ICP患者进行分度诊断和处理 ,有助于改善围产儿预后。     

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。     

克拉玛依地区妊娠肝内胆汁淤积症流行病学调查结果分析

目的　了解本地区妊娠肝内胆汁淤积症(intrahepatic cholestasis of pregnancy, ICP)的发病率及发病特点。　方法　从妊娠20~24周开始普查,动态观察至36周以上,以总胆汁酸酶循环法测定血清总胆汁酸(total bile acid,TBA),TBA>28.5μmol /L为异常,同时复查肝功能加以确诊。　结果　共普查1275例,确诊为ICP 的患者102 例,发病率为8.00%。妊娠33~36 周ICP的发病率(66/351,18.80%)明显高于其他不同孕龄组(P<0.01)。少数民族孕妇ICP的发病率(47/328,14.33%)高于汉族孕妇(55/947, 5. 81%) (P< 0. 01)。有ICP 高危因素的患者ICP 发病(10/67,14.93%)高于无高危因素组(92/208,7.62%)(P<0.01)。　结论　克拉玛依地区ICP的发病率为8 00%,为ICP的高发地区。少数民族孕妇ICP的发病率明显高于汉族发病率。ICP的发病与孕周、孕妇年龄、家族、服药史等有一定的相关性。TAB在整个孕期的波动范围较大。     

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.     

辅助性T淋巴细胞亚型与妊娠期肝内胆汁淤积症发病的关系

目的　探讨辅助性T淋巴细胞 (TH) 1型细胞因子 [γ干扰素 (IFN γ)、肿瘤坏死因子α(TNF α) ]及TH2 型细胞因子 [白细胞介素 4(IL 4) ]与妊娠期肝内胆汁淤积症 (ICP)发病的关系 ,从分子免疫学角度探讨ICP的发病机理。方法　采用双抗体夹心酶联免疫吸附法 ,检测 2 0例ICP孕妇 (研究组 )和 2 0例正常妊娠妇女 (对照组 )外周血单个核细胞在植物血凝素刺激下产生TH1型细胞因子(IFN γ ,TNF α)及TH2 型细胞因子 (IL 4)的水平 ,并对TH1型细胞因子与ICP患者血清总胆汁酸的相关性进行分析。结果　 ( 1)研究组孕妇的IFN γ、TNF α水平分别为 ( 63 9± 15 6)ng/L、( 10 2 1± 2 3 1)ng/L ;明显高于对照组孕妇的 ( 464± 147)ng/L、( 72 8± 175 )ng/L ,两组比较 ,差异有极显著性 (P <0 0 0 1)。研究组孕妇的IL 4水平为 ( 2 2± 4)ng/L ,明显低于对照组孕妇的 ( 2 7± 6)ng/L ,两组比较 ,差异有显著性(P <0 0 5 )。 ( 2 )研究组孕妇的TNF α/IL 4比值为 48± 11,明显高于对照组孕妇的 3 0± 8;研究组孕妇的IFN γ/IL 4比值为 3 0± 8,明显高于对照组的 19± 6,两组分别 ,差异均有极显著性 (P <0 0 0 1)。( 3 )研究组孕妇的IFN γ、TNF α水平与ICP患者血清胆汁酸水平呈正相关 ,相关系数 (r)分别为 0 45 8,0