摘要
目的:探讨妊娠肝内胆汁淤积症(ICP)中人类白细胞抗原G(HLA-G)的表达,Th1/Th2细胞因子的变化,及两者间关系和它们对ICP发生发展的影响,以进一步研究ICP的发病机制,为临床诊治提供新的思路。
方法:选取2007年12月至2008年3月在中南大学湘雅二医院确诊为ICP,行剖宫产终止妊娠的初产妇26例为ICP组,同期在该院行剖宮产的正常初产妇22例作为对照组(NP组)。用免疫组织化学法分别检测两组孕妇胎盘组织HLA-G蛋白的表达,同时用酶联免疫吸附法(ELISA)检测两组孕妇外周血中α肿瘤坏死因子(TNF-α)、白细胞介素-4(IL-4)水平,并测定血清中总胆汁酸(TBA)水平。
结果:1、ICP组孕血中TBA浓度27.05(16.08,44.93)μmol/L明显高于NP组(4.35±2.68)μmol/L(P＜0.01);2、ICP组胎盘组织绒毛外滋养层(EVT)细胞中HLA-G蛋白的表达程度(弱阳性62%,阳性31%,强阳性7%)明显低于NP组(弱阳性14%,阳性18%,强阳性68%)(P＜0.01);3、ICP组胎盘组织HLA-G蛋白表达的平均光密度(MOD)52.91±7.19明显低于NP组69.26±7.72(P＜0.01);4、ICP组孕血TNF-α浓度为(101.31±19.30)pg╱ml明显高于NP组(54.51±23.72)pg╱ml(P＜0.01);ICP组孕血IL-4浓度为(22.16±6.55)pg/ml明显低于NP组(31.69±8.25)pg╱ml(P＜0.01);ICP组TNF-α/IL-4为4.52(3.91,6.07)明显高于NP组(1.72±0.61)(P＜0.01);5、ICP组胎盘组织HLA-G蛋MOD与孕血TNF-α呈负相关(r=-0.987,P＜0.01),与IL-4及TNF-α/IL-4无明显相关性(P＞0.05);6、ICP组中外周血TBA与TNF-α呈正相关(r=0.999,P＜0.01),与胎盘组织HLA-G蛋白MOD呈负相关(r=-1.0,P＜0.01),与IL-4及TNF-α/IL-4无明显相关性(P＞0.05)。
结论:1、ICP胎盘组织中HLA-G蛋白的表达明显降低,这可能是ICP免疫性病因的一部分;2、ICP孕妇外周血中存在Th1型细胞因子增多,Th2型细胞因子减少,Th1/Th2细胞因子失调,向Th1型偏移的现象;3、ICP组胎盘组织HLA-G表达的MOD与外周血TNF-α水平呈负相关,说明由于HLA-G表达的降低导致Th1型细胞因子增多;4、ICP孕妇外周血中TBA浓度与胎盘组织HLA-G表达的MOD呈负相关,与孕血TNF-α水平呈正相关,由此推测HLA-G和Th1型细胞因子参与ICP的发生、发展。
Objective:To investigate the expression of human leukocyte antigen-G(HLA-G)protein and the changes of T-helper 1/T-helper 2 type(Th1/Th2)cytokines in intrahepatic cholestasis of pregnancy(ICP) in order to master their affect on the pathogenity and the development of ICP.
Methods:Peripheral blood and placental tissues were obtained from 26 patients with ICP(ICP group)and 22 normal pregnant women(NP group)in the operation room for Caesarean birth.Immunohistochemistry was used to detect the expression of HLA-G protein in the placental tissues.Meanwhile we tested the concentrations of TNF-αand IL-4 by ELISA in the peripheral blood we got and checked the levels of TBA in the serum.
Results:1.The TBA level of ICP group was 27.05(16.08,44.93)μmol/L which was significant higher than that of NP group (4.35±2.68)μmol/L statistically(P＜0.01).2.The degree of positive expression of HLA-G protein in the EVT cells of placenta of ICP group was significantly lower than that in the NP group statistically(P＜0.01).3. The MOD of positive expression of HLA-G protein in the placenta of ICP group(52.91±7.19)was significantly lower than that in the NP group (69.26±7.72)statistically(P＜0.01).4.The concentration of TNF-α(101.31±19.30)pg/ml in ICP group was significantly higher than that in NP group(54.51±23.72)pg/ml(P＜0.01).However the concentration of IL-4(22.16±6.55)pg/ml in ICP group was lower than that in NP group (31.69±8.25)pg/ml(P＜0.01).So the ratio of TNF-α/IL-4 4.52(3.91,6.07) was higher in ICP group than that in NP group(1.72±0.61)statistically (P＜0.01).5.There was a negative correlation between the MOD of HLA-G protein and TNF-α(r=-0.987,P＜0.01)in the ICP group. However,no correlations with IL-4 and TNF-α/IL-4(P＞0.05).6.There was a positive correlation between TBA and TNF-α(r=0.999,P＜0.01), and a negative correlation between TBA and the MOD of HLA-G protein (r=-1.0,P＜0.01)in the ICP group.However,no correlations with IL-4 and TNF-α/IL-4(P＞0.05).
Conclusions:1.The expression of HLA-G protein in the placental tissues was significantly decreased in patients with ICP,which might be part of the cause of the disease related to immunity.2.There was an increase of Th1 cytokines,and a decrease of Th2 cytokines,so an imbalance in Th1/Th2 cytokines in ICP group,concretely,float to the Th1 type.3.There was a negative correlation between HLA-G and TNF-α, which demonstrated that the decrease of the expression of HLA-G led to the increase of Th1 cytokines.4.There was a negative correlation between TBA and the MOD of HLA-G,however,a positive correlation between TBA and TNF-αin ICP,which showed us that HLA-G and TNF-αmight participate in the occurrence and development of ICP。
引文
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