原发性胆汁性肝硬化患者外周血单个核细胞趋化因子受体的表达及临床意义

Expression and clinical significance of chemokine receptor in peripheral blood mononuclear cells in patients with primary biliary cirrhosis

目的:初步探讨趋化因子受体(chemokine receptor)与原发性胆汁性肝硬化(PBC,primary biliary cirrhosis)发生发展的关系。方法:采用实时荧光定量PCR和流式细胞术,分别从基因转录和蛋白表达水平检测60例PBC、60例乙型肝炎肝硬化患者(疾病对照)和60例健康对照者的外周血单个核细胞(PBMCs)中CCR1、CCR3和CCR5的表达;生化常规测定PBC患者和健康对照者的总胆红素(TBIL)、γ-谷氨酰基转移酶(γ-GT)水平,分析它们与趋化因子之间的相关性。结果:PBC患者PBMCs中的CCR1、CCR3、CCR5的mRNA和蛋白表达均明显低于健康对照组和疾病对照组(P<0.05),而疾病对照组和健康对照组PBMCs中CCR1、CCR3、CCR5 mRNA和蛋白表达无统计学差异(P>0.05);PBC患者Ⅲ、Ⅳ期PBMCs中的CCR1、CCR3、CCR5的mRNA和蛋白表达较Ⅰ、Ⅱ期明显降低(P<0.05);PBC患者CCR1蛋白表达水平与TBIL水平显著负相关(r=-0.445,P<0.01),与γ-GT无线性相关关系(r=-0.230,P>0.05);CCR3蛋白表达水平与TBIL水平无线性相关关系(r=-0.173,P>0.05),与γ-GT水平负相关(r=-0.295,P<0.05);CCR5蛋白表达水平与TBIL、γ-GT水平均负相关(r=-0.531,P<0.01;r=-0.665,P<0.01)。结论:CCR1、CCR3、CCR5的表达与PBC的发生发展存在一定的相关性,可能参与了PBC的调控机制,为PBC的诊断和预防提供了新线索。

Objective：To investigate the relationship of chemokine receptor with the development and progression of primary biliary cirrhosis （PBC）. Methods： Real-time PCR and flow cytometry were used to examine the mRNA and protein expression of chemokine receptor 1 （CCR1）,CCR3 and CCR5 in the peripheral blood mononuclear cells （PBMCs） of 60 patients with PBC,60 patients with hepatitis B-related cirrhosis, and 60 normal controls. Total bilirubin （TBIL） and γ-glutamyltransferase （γ-GT） levels were determined in the patients with PBC and normal controls,and their correlation with chemotactic factors was also analyzed. Results.. Both the mRNA and protein expression levels of CCR1 ,CCR3 and CCR5 in the PBMCs were significantly lower in PBC patients than those in the other two groups （P〈0. 05）, and there were no significant differences between the latter two groups. The mRNA and protein levels of CCR1, CCR3 and CCR5 were significantly lower in patients with stage Ⅲ and Ⅳ PBC than those with stage Ⅰ and Ⅱ PBC. CCR1 protein expression was correlated with TBIL levels in PBC patients（r=- 0. 445, P〈0. 01 ）, but not with γ-GT（r=-0. 230, P〉0.05）. CCR3 protein was not linearly correlated with TBIL level （r=- 0. 173, P〉0. 05）, but was correlated with γ-GT（r= -0. 295, P〈 0.05）. Expression of CCR5 protein was negatively correlated with both TBIL and γ-GT levels（r= -0. 531, P〈0.01; r= -0. 665, P 〈0. 01） Conclusion： CCR1, CCR3 and CCR5 expression is associated with the development and progression of PBC; they may be involved in the regulatory mechanism of PBC, which may cast new lights on the diagnosis and prevention of PBC.