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目的：研究妊娠期肝内胆汁淤积症患者外周血中维生素D 受体的表达与Th1/Th2 型细胞因子干扰素-γ / 白细胞介素-4 （IFN-γ/IL-4）的变化关系，探讨ICP 发病机制。方法：选取ICP 患者31 例（ICP 组），孕周相匹配的正常孕妇31 例（正常对照组）。采用酶联免疫吸附试验（ELISA 法），检测两组孕妇血清中Th1 型细胞因子(IFN-γ)和Th2 型细胞因子(IL-4)的水平；采用实时荧光定量逆转录- 多聚酶链反应（qRT-PCR），检测两组孕妇外周血单个核细胞维生素D 受体（VDR）mRNA 的表达水平，采用3- 磷酸甘油醛脱氢酶（GAPDH）为内参，根据相对定量公式：2-△△CT 分析VDR mRNA 的表达水平。结果：（1）ICP 组外周血清中IFN-γ 的浓度[(230.93±36.04)pg/ml]明显高于正常对照组[(138.37±25.08)pg/ml]，差异有统计学意义(P<0.01)。ICP 组血清中IL-4 浓度 [(9.99±3.19)pg/ml]和正常对照组[(8.58±2.43)pg/ml]比较，差异无统计学意义(P>0.05)。ICP 组IFN-γ/IL-4 比值(24.56±6.91)高于正常对照组(17.13±4.84)，差异有统计学意义(P<0.05)。（2）ICP 组外周血单个核细胞维生素D 受体mRNA 的表达明显低于正常对照组(P<0.01)，正常对照组VDR 的表达定义为1.0，ICP 组的表达量为0.4。（3）ICP 组外周血中VDR 的表达水平与IFN-γ 浓度呈明显负相关(r= -0.833，P<0.01)，与IL-4 浓度无明显相关(r=-0.109，P>0.05)，与IFN-γ/IL-4 比值呈负相关，但相关性不强 (r=-0.356，P =0.049<0.05)。结论：ICP 患者外周血Th1/Th2 型细胞因子平衡由Th2 向Th1 偏移，可能与ICP 孕妇外周血单个核细胞VDR 的表达减少有关。

英文摘要:

Objective: To study the relationship between the expression of the vitamin D receptor (VDR) and Th1/Th2 cytokines （IFN-γ/IL-4）profile in the peripheral blood of patients with intrahepatic cholestasis of pregnancy (ICP),so as to investigate the pathogen of ICP. Methods: There were 31 pregnant women with intraheptic cholestasis of pregnancy and 31 normal pregnant women in the study. The T helper cell type-1 (Th1) cytokine [interferon-gamma (IFN-γ)] and T helper cell type-2 (Th2) cytokine [interleukin-4 (IL-4)] in the serum of patients with ICP (ICP group)and normal pregnant women (normal group,NP) were measured by enzyme linked immuno-sorbent assay (ELISA);The vitamin D receptor (VDR) expression in the peripheral blood mononuclear cells(PBMCs) was examined by real time fluorescent quantitative reverse transcriptase polymerase chain reaction（real-time qRT-PCR）in the two groups. Glyceraldehyde-3-phosphate Dehydrogease (GAPDH) was used as an endogenous reference. VDR expression level were used by the 2-△△CT method in the two group. Results: (1)The concentrations of IFN-γ in ICP group [(230.93±36.04)pg/ml] was significantly higher than those in normal group [ (138.37±25.08)pg/ml]( P<0.01). But there were no significant differences in the concentrations of IL-4 between ICP group [(9.99±3.19) pg/ml] and normal group [(8.58±2.43)pg/ml] (P>0.05).The IFN-γ/IL-4 ratio in ICP group(24.56±6.91) was higher than those in normal group(17.13±4.84) (P<0.05). (2)VDR expression in the peripheral blood mononuclear cells was found to be significantly lower(0.4) in all patients with ICP than that in normal pregnancy (1.0),P<0.01.(3)In ICP group the correlation between the expression of VDR and the levels of IFN-γ was significantly negative (r= -0.833,P<0.01); the correlation between the expression of VDR and the levels of IL-4 was not significant(r= -0.109,P>0.05); the correlation between the expression of VDR and IFN-γ/IL-4 ratio was negative, but the relation was not significant (r= -0.356,P=0.049<0.05). Conclusions: The cytokine profile shift from Th2-type to Th1-type in the peripheral blood, which may relate to the reduced expression of VDR in the peripheral blood mononuclear cells of the patients with ICP.

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