妊娠期肝内胆汁淤积症发病机制研究进展

妊娠期肝内胆汁淤积症(ICP)是妊娠中晚期特有的并发症,其发病部位在母体,而主要危害胎儿.ICP发病机制可以从母体和胎儿两个层面来研究,这两个层面有内在联系也有各自病理生理特点,在这两个层面中,分别存在多种因素的作用.母体方面,在一定遗传背景下,雌激素作用通路的异常反应,是研究的主要方向;胎儿方面,胎盘结构和功能改变及其所带来的影响,应成为研究ICP对胎儿危害机制需要关注的重要内容.     

妊娠期肝内胆汁淤积症发病机制研究进展

妊娠期肝内胆汁淤积症（ICP）是妊娠中晚期特有的并发症，其发病部位在母体，而主要危害胎儿。ICP发病机制可以从母体和胎儿两个层面来研究，这两个层面有内在联系也有各自病理生理特点，在这两个层面中，分别存在多种因素的作用。母体方面，在一定遗传背景下，雌激素作用通路的异常反应，是研究的主要方向；胎儿方面，胎盘结构和功能改变及其所带来的影响，应成为研究ICP对胎儿危害机制需要关注的重要内容。     

妊娠期肝内胆汁淤积症发病的分子机制研究进展

妊娠期肝内胆汁淤积症(ICP)发病机制尚不清楚,多数研究认为激素和遗传因素起重要作用.近年遗传性肝内胆汁淤积性疾病的研究取得重大进展,已确认若干胆淤基因如ABCB4、ABCB11及ATP8B1等.这些基因在ICP发病机制中所起的作用已引起关注.     

妊娠期肝内胆汁淤积症发病的分子机制研究进展

妊娠期肝内胆汁淤积症(ICP)发病机制尚不清楚，多数研究认为激素和遗传因素起重要作用。近年遗传性肝内胆汁淤积性疾病的研究取得重大进展，已确认若干胆淤基因如ABCB4、ABCB11及ATP881等。这些基因在ICP发病机制中所起的作用已引起关注。     

妊娠期肝内胆汁淤积症的研究进展

妊娠期肝内胆汁淤积症(ICP)是一种妊娠期特有肝脏疾病,其临床特点包括瘙痒、肝酶和血清胆汁酸水平升高。ICP通常发生在妊娠晚期,并于分娩后迅速消失。ICP病因是多因素的,遗传、内分泌及环境因素在其发病机制中相互作用。ICP的孕产妇结局通常是良性的,而胎儿并发症如早产、羊水粪染、胎儿窘迫和突然的不可预测的胎儿宫内死亡导致围产儿发病率和死亡率显著增加。熊去氧胆酸是目前治疗ICP最安全有效的药物。ICP的管理主要包括孕产妇肝功能与血清胆汁酸水平的监测,同时还包括评估胎儿安全性,并在完成促胎肺成熟后决定适时分娩。本文根据最近的文献资料综述了ICP最新的研究进展。     

妊娠期肝内胆汁淤积症的研究进展

妊娠期肝内胆汁淤积症（ICP）是妊娠中、晚期特发性肝脏疾病。由于血清胆汁酸升高,在临床上表现为以皮肤瘙痒和黄疸为特征,主要危害胎儿,出现胎儿窘迫、死胎、早产及其他新生儿并发症。ICP的病因和发病机制尚不明确。本文从遗传、激素和环境因素方面探讨了ICP的发病机制,通过胆汁酸对胎儿的影响,了解其对胎儿危害的机制,为临床上治疗ICP奠定基础。     

妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症 (ＩＣＰ)是一种重要的妊娠并发症 ,它以妊娠期出现皮肤瘙痒和黄疸为特点 ,可导致胎儿宫内窘迫、早产、死胎、死产 ,使围产儿病率和死亡率增加 ,已引起产科医师的广泛关注。一、病因及发病机理ＩＣＰ的发病原因尚未十分明了 ,通过大量研究认为其发病可能与下列因素有关。1.雌激素 :不少学者认为 ,ＩＣＰ与妊娠时血中雌激素水平增高或对雌激素过度敏感有关。雌激素化学结构式中的Ｃ 17被烷化后 ,可提高它损害肝脏的能力。Ｒｅｙｅｓ,Ｓｉｍｏｎ[1] 总结了众多的胆汁淤积动物模型研究后指出 ,雌激素导致胆汁淤积可能通过…     

妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症的特点是妊娠晚期出现皮朊瘙关及肝内胆汁淤积。其发病机理是因遗传家族及环境等因素使肝脏对雌激素及其代谢产物产生过强反应，导致肝脏状隙脂质膜流动性减少，Ｎａ＾＋，Ｋ＾＋，－ＡＴＰ酶活性降低而产生胆汁淤积。     

妊娠期肝内胆汁淤积症的研究进展

妊娠期肝内胆汁淤积症(ICP)是性激素、家族遗传、免疫、环境等多因素相互作用的结果；高浓度胆汁酸引起胎盘、脐血管异常收缩进而使胎儿宫内急性缺氧。及早发现病情并了解严重程度，辅以综合的药物治疗，加强母儿监测，适时结束妊娠可改善母儿不良处境。     

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...     

妊娠期肝内胆汁淤积症胎盘组织中OATP-A基因表达的研究

目的:探讨有机阴离子转运多肽OATP-A在正常晚孕妇女及ICP孕妇胎盘组织的表达水平及意义。方法:收集正常晚孕胎盘组织(对照组)、轻度ICP胎盘组织及重度ICP胎盘组织各10例。采用免疫组化、Western blot分别检测胎盘组织中OATP-A的组织学定位及蛋白表达水平。结果:正常组及ICP组胎盘组织中OATP-A表达均定位于胎盘滋养细胞的细胞膜,血管内皮无表达。对照组、ICP轻度组及ICP重度组的OATP-A蛋白表达量分别为0.21±0.02、0.53±0.04、0.79±0.12,ICP轻度组及重度组OATP-A蛋白表达量均高于对照组,两两比较,均有统计学意义(P<0.05)。结论:ICP胎盘组织中OATP-A表达明显升高,可能是对抗胆汁淤积的一种保护性反应,对降低胎儿部分胆汁酸及胆红素水平有重要作用。     

The role of genetic mutations in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder of pregnancy characterized by pruritus, elevated liver enzymes and fasting serum bile acids. Genetic predisposition has been suggested to play a role in its etiology and mutations in the ATP8B1(OMIM 1602397) (FIC1), ABCB11(OMIM 1603201) (BSEP), and ABCB4(OMIM 1171060) (MDR3) genes have been implicated.In the present study, we aimed to investigate the possible role of ATP8B1, ABCB11, and ABCB4 gene mutations in the patients with ICP.Materials and methodsA total of 25 patients who were diagnosed with ICP were included in the study. Genetic test results and mutation status of the patients as assessed by the next-generation sequencing technology were retrospectively retrieved from the hospital database.ResultsOf all patients, significant alterations in the ATP8B1 (n = 2), ABCB11 (n = 1), and ABCB4 (n = 7) genes were observed in 10 patients using the molecular analysis testing. All these alterations were heterozygous. Of these alterations, four were reported in the literature previously, while six were not. Using the in-silico parameters, there was a pathogenic alteration in the ABCB4 gene in one patient, while there was no clinically relevant alteration in the other gene mutations in the remaining nine patients.ConclusionConsidering the fact that the alterations were compatible with clinical presentations of the ICP patients and the incidence of these mutations is low in the general population, we believe that our study results are clinically relevant. Further molecular genetic tests in ICP patients and functional studies supporting the results would shed light into the clinical importance of these alterations.     

Alpha-hydroxybutyrate dehydrogenase activity in intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is associated with increased perinatal mortality and morbidity. Alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) is an enzyme that originates in the cytoplasm of hepatocytes and can be detected in the serum. The aim of this study was to determine the characteristics of alpha-HBDH activity in ICP. METHODS: The study included 100 women in their third trimester of pregnancy, 58 of whom had ICP (the study group) and 42 were healthy (the control group); another group, 26 nonpregnant women, was also analyzed to follow changes in alpha-HBDH activity during pregnancy. The concentrations or activity of fractionated bilirubin; bile acids; total alkaline phosphatase; alanine and aspartate aminotransferases; total high-density and low-density lipoprotein cholesterol; triglycerides; total protein; and alpha-HBDH were assessed. RESULTS: The activity of serum alpha-HBDH is increased during the third trimester of pregnancies complicated by ICP, and it correlates positively with total and direct bilirubin concentration and total alkaline phosphatase activity. CONCLUSIONS: Alpha-hydroxybutyrate dehydrogenase serum activity seems to be another biochemical parameter useful in the assessment of ICP severity.     

熊去氧胆酸治疗妊娠期肝内胆汁淤积症

目的：评估熊去氧胆酸（ＵＤＣＡ）治疗妊娠期肝内胆汁淤积症（ＩＣＰ）的效果。方法：选择６０例ＩＣＰ病人，分成两组，观察组（ｎ＝３０）采用ＵＤＣＡ１００ｍｇ每日３次，对照组（ｎ＝３０）采用黄疸茵陈冲剂２０ｇ每日３次，观察治疗效果。结果：观察组瘙痒评分治疗１周后明显下降，血ＡＬＴ、ＴＢＡ、ＣＨＯ、ＴＧ池明显下降（Ｐ〈０．０５），而对照组下降缓慢，同时还发现观察组产时缺氧发生率低，孕周较长，新生儿体重较重     

腺苷蛋氨酸对妊娠肝内胆汁淤积症的临床观察

目的：评估腺苷蛋氨酸治疗妊娠肝内胆汁淤积症（ICP）的效果。方法：观察组30例采用腺苷蛋氨酸治疗,对照组30例采用苦黄注射液治疗,治疗3周后观察功能、瘙痒评分,两组病人在孕32例周后行NST检查,分后比较两组围生儿预后及产妇预,后情况。结果：观察组血清总胆红素（TBIL）、直接胆红素（DBIL）、血清总胆汁酸（TBA）、碱性磷酸酶（ALP）、血清总胆固醇（CHOL）及瘙羊评分明显下降,与对照组比较差异有显著性意义（P＜0．01）,观察组产时缺氧发生率低,且孕周较长、新生儿体重较重,剖宫产率较低（P＜0．05）。结论腺苷蛋白氨酸是治疗ICP的有效药物。     

The role of interleukin-17 in intrahepatic cholestasis of pregnancy

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease, is characterized by pruritus, abnormal liver function and elevated serum bile acid levels. The main cause of ICP has not yet been identified. We aimed to provide a new perspective to the pathogenesis of by investigating the possible association of circulating interleukin-17 (IL-17) that is a recently discovered proinflammatory cytokine levels with ICP.

Materials and methods: In this controlled cross-sectional study, maternal venous blood samples were obtained from 33 consecutive pregnant women with ICP (15 with mild and 18 with severe forms of the disease) and 25 healthy women with uncomplicated pregnancies (as the control group) and IL-17 levels were compared among the groups.

Results: Although serum IL-17 levels were significantly higher in the severe ICP group than in the control group (p?=?0.022), there were no significant differences between the mild and severe ICP groups or between the control and mild ICP groups.

Conclusion: Explaining the mechanisms of hepatocyte injury might contribute to the existing therapeutic strategies for treating cholestatic diseases. Changes in IL-17 levels may shed light on the pathogenesis of ICP.     

妊高征及妊娠期肝内胆汁淤积症患者血浆肝素水平测定及其变化

目的　探讨妊娠晚期孕妇血浆肝素水平降低对妊高征、妊娠期肝内胆汁淤积症 (ICP)发生的影响。方法　对 1 999年 1 0月至 2 0 0 0年 1 0月 70例孕妇用生色法测定血浆肝素 ,并同时测定血小板数与血浆纤维蛋白原水平。其中妊高征组 2 0例、ICP组 2 0例、正常妊娠组 30例。随机选取 30例非孕妇女作对照组。结果　三组孕妇血浆肝素水平均明显低于对照组 (P <0 0 5 ) ,妊高征组显著性低于正常妊娠组和ICP组 (P <0 0 1 ) ;正常妊娠组血小板数量明显低于对照组 (P <0 0 1 ) ,但其与妊高征组及ICP组的比较差异均无显著性 (P >0 0 5 ) ;三组孕妇血浆纤维蛋白原水平均极显著性高于对照组 (P <0 0 1 )。结论　随着妊娠终止 ,血浆中肝素和血小板随之恢复至正常范围。而妊高征患者产后血浆肝素尚未达到正常水平范围 ,说明该病的病理生理变化与血浆中肝素水平降低可能有关     

Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies

Objective: To describe perinatal outcomes of twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP).

Methods: We conducted a retrospective cohort study of women delivered at a large tertiary obstetric center in Shanghai, China from January 2006 to May 2014. Delivery data were abstracted from medical records of all twin gestations delivered at the hospital.

Results: A total of 129/1922(6.7%) twin and 1190/92?273 singleton (1.3%) pregnancies were complicated by ICP. An increased risk of stillbirth among twin pregnancies was observed (3.9% and 0.8% in the ICP and non-ICP groups, respectively; aOR 5.75, 95% CI 2.00–16.6). Stillbirths with ICP and twins occurred between 33 and 35 weeks gestation compared to 36–38 weeks gestation among singletons. ICP in twins was also associated with an increased risk of preterm birth (<37 weeks) with an aOR of 4.17 (95% CI 2.47–7.04) and an aOR of 1.89 (95% CI 1.26–2.85) for delivery <35 weeks. Twin pregnancies complicated by ICP also had increased meconium staining of amniotic fluid and lower birth weight.

Conclusions: Twin pregnancies with ICP have significantly increased risks of adverse perinatal outcomes including stillbirth and preterm birth. Stillbirth occurs at an earlier gestational age in twin gestation compared to singletons, suggesting that earlier scheduled delivery should be considered in these women.     

Placental proteome alterations in women with intrahepatic cholestasis of pregnancy

Objective

To investigate differences in the placental proteomes of women with intrahepatic cholestasis of pregnancy (ICP) and those with a normal pregnancy.

Methods

Ten pregnant women diagnosed with ICP were recruited at the First People’s Hospital of Yuhang District from October 2011 to September 2012; 10 age-matched healthy pregnant women acted as controls. Total placental proteins were extracted and subjected to two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry to identify proteins that were differentially expressed in the two groups.

Results

In total, 37 protein spots with differentially expressed proteins were found. These comprised proteins involved in cytoskeleton activity, blood coagulation, and platelet activation as well as chaperones, heat shock proteins, RNA-binding and calcium-binding proteins, and various enzymes.

Conclusion

The placentas of women with ICP displayed significant proteome differences compared with women with a normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of ICP. Further verification and research are required to elucidate the exact roles of these proteins in ICP pathogenesis.