原发性胆汁性肝硬化患者单核细胞内miR-302e表达降低及意义

目的 研究miR-302e在原发性胆汁性肝硬化发病机制中的作用。方法 采用荧光定量PCR技术检测了10名选健康对照者和12名PBC患者的T细胞（CD3+），B细胞（CD19+）及单核细胞（CD14+）内miR-302e的相对表达量。以100ng/mL的LPS刺激PBC患者、健康个体的单核细胞以及转染了miR-302e mimics或inhibitor的THP-1细胞、，24小时后采用ELISA法检测培养基内IL-6及TNF-α浓度的变化。结果 PBC患者外周血单核细胞内miR-302e的表达量较健康个体显著降低（P<0.001）。在LPS刺激的THP-1细胞中， miR-302e mimics和inhibitor分别可以抑制和促进IL-6和TNF-α的释放（P<0.05）。在LPS刺激下，PBC患者单核细胞释放IL-6及TNF-α的能力显著强于来自健康个体的单核细胞（P<0.05）。结论 miR-302e表达降低可能是导致其单核细胞对LPS刺激呈现高反应性的原因，miR-302e可能通过这种途径参与了PBC的发病机制。

Decreased miR-302e expression in monocytes of patients with primary biliary cirrhosis and its significance

Objective To investigate the role of miR-302e in the pathogenesis of primary biliary cirrhosis(PBC).Methods The relative expression levels of miR-302e in T cells(CD3+),B cells(CD19+) and monocyte(CD14+) of 10 healthy controls and 12 PBC patients were detected by RT-PCR.The THP-1 cells transfected with miR-302e mimics or inhibitors and the monocytes from PBC patients and healthy controls were treated with 100 ng/ml bacteria lipopolysaccharide(LPS).Twenty-four hours later,the concentrations of IL-6 and TNF-α in the culture medium were measured by ELISA.Results The monocytes of PBC patients had a significantly lower miR-302e expression compared to those of healthy controls(P<0.01).miR-302e inhibitors significantly enhanced the production of IL-6 and TNF-α in THP-1 cells exposed to LPS,and miR-302e mimics significantly decreased their production(P<0.05).When treated with LPS,the monocytes from PBC patients produced significantly more IL-6 and TNF-α compared to those from healthy controls(P<0.05).Conclusion Decreased miR-302e expression in monocytes of PBC patients may enhance IL-6 and TNF-α production and thus participate in the pathogenesis of PBC.