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.

Relationship between total bile acid concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy

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.