原发性胆汁性胆管炎患者维生素D受体表达降低对免疫反应影响的研究

Effect of Low Expression of Vitamin D Receptor on Immune Response in Patients With Primary Biliary Cholangitis

背景:免疫作用在原发性胆汁性胆管炎(PBC)的发生中起有关键作用,维生素D通过维生素D受体(VDR)发挥免疫调节作用,可能参与PBC的发生和发展。目的:探讨PBC患者VDR表达降低对免疫反应的影响。方法:选取30例PBC患者,以30例非PBC患者作为对照。以实时定量PCR法检测肝脏组织和外周血单个核细胞(PBMC)中VDR、SOCS-1、miR-155 mRNA表达,蛋白质印迹法和免疫组化法检测VDR、SOCS-1蛋白表达。比较对照组和PBC患者肝脏组织以及PBMC中VDR、SOCS-1和miR-155表达情况,并分析PBC患者肝脏组织VDR、SOCS-1和miR-155表达的相关性。结果:与对照组相比,PBC患者肝脏组织VDR、SOCS-1 mRNA和蛋白表达均显著降低(P <0. 05),miR-155 mRNA表达显著升高(P <0. 05); PBMC中VDR、SOCS-1 mRNA和蛋白表达均显著降低(P <0. 05)。PBC患者肝脏组织VDR蛋白与SOCS-1表达水平呈正相关,miR-155表达与VDR、SOCS-1表达水平均呈负相关。结论:PBC患者VDR表达显著降低,其可能通过miR-155和SOCS-1参与PBC发生、发展的调控。

Background:Immune function plays a key role in the development of primary biliary cholangitis(PBC).Vitamin D plays an immunomodulatory role through vitamin D receptor(VDR)and may participate in the development and progression of PBC.Aims:To investigate the effect of low expression of VDR on immune response in patients with PBC.Methods:Thirty patients with PBC were enrolled,and 30 patients with non-PBC were served as controls.mRNA expressions of VDR,SOCS-1,miR-155 in liver tissue and peripheral blood mononuclear cell(PBMC)were detected by real-time quantitative PCR,protein expressions of VDR,SOCS-1 were measured by Western blotting and immunohistochemistry.Expressions of VDR,SOCS-1 and miR-155 in liver tissue and PBMC were compared between PBC group and control group.Correlations of expressions of VDR,SOCS-1 and miR-155 in liver tissue in patients with PBC were analyzed.Results:Compared with control group,mRNA and protein expressions of VDR and SOCS-1 were significantly decreased(P<0.05),and expression of miR-155 in liver tissue was significantly increased in PBC patients(P<0.05).The mRNA and protein expressions of VDR and SOCS-1 in PBMC were significantly decreased in PBC group than in control group(P<0.05).There was a significant positive correlation between VDR protein and SOCS-1 expression and a negative correlation between expressions of miR-155 and VDR,SOCS-1 in liver tissue of PBC patients.Conclusions:The expression of VDR in patients with PBC is significantly decreased.VDR may be involved in the regulation of development and progression of PBC through miR-155 and SOCS-1.