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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
刘晓1△,胡志德2,邓安梅2*,仲人前1*
0
(1. 第二军医大学长征医院实验诊断科, 上海200003
2. 第二军医大学长海医院实验诊断科, 上海
共同第一作者
*通信作者200433)
摘要:
目的 探讨miR-302e在原发性胆汁性肝硬化(PBC)发病机制中的可能作用。方法 采用荧光定量PCR技术检测了10名健康对照者和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100 ng/ml的LPS刺激PBC患者、健康个体的单核细胞及转染了miR-302e mimics或inhibitor的THP-1细胞,24 h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降低(P<0.01)。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、TNF-α的释放(P<0.05)。在LPS刺激下,PBC患者单核细胞释放IL-6、TNF-α的能力强于来自健康个体的单核细胞(P<0.05)。结论 miR-302e表达降低可能导致单核细胞对LPS刺激呈现高反应性,从而参与PBC发病。
关键词:  微RNAs  胆汁性肝硬化  单核细胞  炎症
DOI:10.3724/SP.J.1008.2012.0160
投稿时间:2011-11-26修订日期:2012-02-10
基金项目:国家自然科学基金(30972730,81072479,81170263), 上海市科委基金(08QH14001,09JC1405400).
Decreased miR-302e expression in monocytes of patients with primary biliary cirrhosis and its significance
LIU Xiao1△,HU Zhi-de2,DENG An-mei2*,ZHONG Ren-qian1*
(1. Department of Laboratory Diagnosis, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
2. Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Co-first authors.
*Corresponding authors.)
Abstract:
Objective To investigate the role of miR-302e in the pathogenesis of primary biliary cirrhosis (PBC). MethodsThe 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. ResultsThe 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). ConclusionDecreased miR-302e expression in monocytes of PBC patients may enhance IL-6 and TNF-α production and thus participate in the pathogenesis of PBC.
Key words:  microRNAs  biliary liver cirrhosis  monocytes  inflammation