妊娠肝内胆汁淤积症患者胎盘组织HLA-G蛋白表达及其对外周血Th1/Th2细胞因子的影响

Expression of HLA-G protein in placental tissues and its influence on Th1/Th2 cytokines in peripheral blood in patients with intrahepatic cholestasis of pregnancy

目的:探讨人类白细胞抗原G(HLA-G)和Th1/Th2细胞因子在妊娠肝内胆汁淤积症(ICP)中的表达变化及其与ICP发病的相关性。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,同期在该院行剖宫产的正常初产妇22例作为对照(NP)组。用免疫组织化学法检测孕妇胎盘组织HLA-G蛋白的表达,同时用酶联免疫吸附法(ELISA)检测孕妇外周血中肿瘤坏死因子α(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:ICP组孕妇外周血中TBA浓度为(27.05±6.08)μmol/L,明显高于NP组(4.35±2.68)μmol/L(P<0.01);ICP组胎盘组织绒毛外滋养层细胞(EVT)中HLA-G蛋白的表达程度(弱阳性61.54%,阳性30.77%,强阳性7.7%),明显低于NP组(弱阳性13.64%,阳性18.19%,强阳性68.19%)(P<0.01);ICP组胎盘组织HLA-G蛋白表达的平均光密度(MOD)值52.91±7.19,明显低于NP组69.26±7.72(P<0.01);ICP组中TNF-α水平(101.31±19.30)pg/mL,明显高于NP组(54.51±23.72)pg/mL(P<0.01);ICP组IL-4水平(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±1.91)明显高于NP组(1.72±0.61)(P<0.01);ICP组中HLA-G表达的MOD值与TNF-α呈负相关(r=-0.98,P<0.01),与IL-4及TNF-α/IL-4无明显相关性(P>0.05);ICP组中TBA与TNF-α呈正相关(r=0.99,P<0.01),与HLA-G表达的MOD值呈负相关(r=-1.00,P<0.01),与IL-4及TNF-α/IL-4无明显相关性(P>0.05)。结论:ICP患者外周血存在Th1/Th2细胞因子失衡,向Th1偏移的现象;其胎盘组织中HLA-G的表达下降,外周血中Th1型细胞因子增多,可能是ICP肝脏损害的原因之一。

Objective To investigate the changes of human leukocyte antigen-G（HLA-G）protein expression and Th1/Th2 type cytokines in intrahepatic cholestasis of pregnancy（ICP）and their relativity to the etiology of ICP.Methods Peripheral blood and placental tissues were obtained from 26 ICP patients（the ICP group）and 22 normal pregnant women（the NP group）in the operation room for Cesarean birth.Immunohistochemistry was used to detect the expression of HLA-G protein in the placental tissues.Meanwhile we tested the concentrations of tumor necrosis factor-α（TNF-α）and interleukin-4（IL-4）by enzyme-linked immunosorbent assay（ELISA）in the peripheral blood and checked the levels of TBA in the serum.Results TBA level in the ICP group was（27.05±6.08）μmol/L,significant higher than that in the NP group（4.35±2.68）μmol/L（P〈0.01）.The positive expression of HLA-G protein in extravillous trophoblast in the ICP group was significantly lower than that in the NP group（P〈0.01）.The mean optical density（MOD）of positive expression of HLA-G protein in the placenta tissues in the ICP group（52.91±7.19）was significantly lower than that in the NP group（69.26±7.72）（P〈0.01）.The concentration of TNF-α was significantly higher in the ICP group（101.31±19.30）pg/mL than that in the NP group（54.51±23.72）pg/mL（P〈0.01）.The concentration of IL-4 was lower in the ICP group（22.16±6.55）pg/mL than that in the NP group（31.69±8.25）pg/mL（P〈0.01）.The ratio of TNF-α/IL-4 was higher in the ICP group（4.52±1.91）than that in the NP group（1.72±0.61）（P〈0.01）.There was a negative correlation between the MOD of HLA-G protein and TNF-α（r=-0.98,P〈0.01）in the ICP group.No correlation with IL-4 and TNF-α/IL-4 was seen（P〈0.05）.There was a positive correlation between TBA and TNF-α（r=0.99,P〈0.01）,and a negative correlation between TBA and the MOD of HLA-G protein（r=-1.00,P〈0.01）in the ICP group.No correlation with IL-4 and TNF-α/IL-4 was seen（P〈0.05）.Conclusion There is an imbalance of Th1/Th2 cytokines to the Th1 type in the peripheral blood of ICP patients.The expression of HLA-G protein in the placenta of ICP patients decreases,leading to an increase of Th1 type cytokines that may be one of the reasons for liver destroy in ICP.