| Objective: The study was designed to observe the expression of second mitochondria-derived activator of caspases(Smac/DIABLO)and X-linked inhibitor of apoptosis protein(XIAP)in placental trophoblasts between patients with intrahepatic cholestasis of pregnancy(ICP)and normal pregnant women.Furthermore,the correlation between them were analyzed to investigate the important function of mitochondrial signaling pathways for trophoblast apoptosis in the pathogenesis of ICP and provide support for further studies of ICP pathogenesis and its prevention and treatment.Methods: 60 patients with ICP who were treated and delivered in our hospital from October 2015 to August 2016 were divided into 2 groups,mild ICP group(30 cases)and severe ICP group(30 cases)by severity.30 additional cases without ICP who received C-section for termination of pregnancy during the same period were selected as a control group,and all three groups underwent C-section for termination of pregnancy prior to uterine contraction.The placental tissue samples were collected from all the subjects in three groups.The expression of Smac/DIABLO and XIAP in placental trophoblasts was assayed with immunohistochemistry(one-step method)method,and the results were tested using chi-square test for mild ICP group,severe ICP group and control group,respectively,meanwhile,Spearman correlation analysis was adopted to analyze the expression of Smac/DIABLO and XIAP,and t test was adopted for gestational weeks,ages,neonatal Apgar scores and birth weights in the two groups.Results:(1)Smac/DIABLO and XIAP were widely found in the cytosol of ICP placental trophoblasts and normal ones;(2)for the expression of Smac,both mild and severe ICP group showed significantly high results in the placenta tissue as compared with control group,while the expression in severe ICP group was higher than that in mild group,which was statistically significant(P< 0.05);for the expression of XIAP,both mild and severe ICP group showed significantly low results as compared with control group,while the expression in severe ICP group was lower than that in mild group and the difference was statistically significant(P<0.05);(3)in ICP groups,Smac/DIABLO and XIAP were negatively correlated regarding the expression in placental trophoblasts,which was statistically significant(r =-0.914,P< 0.05);(4)No significant difference was observed between ICP groups and control group about mean age.For mean gestational week,there was no significant difference between mild ICP group and control group,severe ICP showed significantly lower results than that in mild group and control group;(5)for neonatal Apgar score,there was no significant difference between two groups,but the average birth weight in ICP group was significantly lower than that in control group,and the difference was statistically significant(P< 0.05).Conclusions: 1.Both Smac/DIABLO and XIAP were expressed in the cytosol of placental trophoblasts in ICP groups and normal control group,suggesting that Smac/DIABLO and XIAP were widely present in human placental trophoblasts.2.In ICP groups,the expression of Smac/DIABLO was higher than that of control group,and the expression of XIAP was lower than that of control group.3.For ICP patients,the expression increased for Smac/DIABLO and decreased for XIAP in high bile acid environment.Oxidative stress and apoptosis could be induced by them through mitochondrial signalpathway and both of the mechanisms may be jointly involved in the occurrence of ICP and adverse pregnancy outcomes.4.In ICP placental trophoblasts,Smac/DIABLO and XIAP were negativelycorrelated regarding expression.Smac/DIABLO interacted with XIAP in mitochondria,indicating that the mutual regulation between Smac/DIABLO and XIAP and themitochondrial apoptotic signal pathway were closely related to theoccurrence and development of ICP,which provided support for the research direction of ICP and its prevention and treatment. |
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