原发性胆汁性肝硬化患者miR-let-7b的异常表达及其意义  

Abnormal expression of miR-let-7b in primary biliary cirrhosis and its clinical significance

作　　者：钱琤 任传路 陈孙孝[2] 仲人前[2] 秦琴[3] 邓安梅[3] 

机构地区：[1]解放军第一ОО医院检验科,苏州215007 [2]上海长征医院实验诊断科 [3]上海长海医院实验诊断科

出　　处：《中华肝脏病杂志》2013年第7期533-536,共4页Chinese Journal of Hepatology

基　　金：基金项目：国家自然科学基金（30972730、30772017）;上海市科委基金（09JCl405400、11JC1410902）

摘　　要：目的探讨原发性胆汁性肝硬化（PBC）患者外周血单个核细胞（PBMC）microRNA（miR—let-7b）的表达及其临床意义。方法以60例PBC患者和35名健康对照者作为研究对象，应用荧光定量RT-PCR方法检测miR-let-To的表达。分析miR-let-7b）与Mayo风险评分及临床分期的相关性。检测PBC患者血清白细胞介素18、总胆红素、碱性磷酸酶、y-谷氨酰转移酶的水平，分析其与miR-let-7b的相关性。独立样本数据比较用非参数Mann-Whitney检验;相关分析采用Spearman相关性检验。结果PBC患者的PBMC miR-let-7b的相对表达水平显著低于健康对照者，差异有统计学意义（0．096±0．047与1．000±0．293，Z=-8．101，P〈0．01）。Ⅱ、Ⅲ、IV期PBC患者PBMCmiR-let-7b的相对表达水平显著低于Ⅰ期患者，与Ⅰ期比较，q值分别为7．697，7．075，12．07，P值均〈0．01;IV期患者显著低于Ⅱ、Ⅲ期患者，q值分别为6．499和4．423，P值均〈0．01。PBC患者PBMCmiR-let-7b的相对表达水平与Mayo风险评分呈负相关（r=-0．4930，P〈0．01），与白细胞介素18（r=-0．4643，P〈0．01）、碱性磷酸酶（r=-4119，P〈0．01）水平也呈负相关，与总胆红素、y-谷氨酰转移酶无明显相关陛。结论PBC患者PBMC miR-let-7b）表达水平显著降低，与疾病进程呈负相关，这为今后PBC的诊断和预防提供了新的线索。To evaluate the expression of microRNA （miR）-let-7b in peripheral blood cells of patients with primary biliary cirrhosis （PBC） and investigate its relationship to clinical disease parameters. Methods Peripheral blood and serum samples were obtained for study from 60 PBC patients and 60 healthy controls. Peripheral blood cells were extracted and subjected to real-time PCR to measure miR-let-7b expression. Serum levels of interluekin （IL）-18, total bilirubin （TBIL）, alkaline phosphatase （ALP）, and gamma-glutamyl transferase （GGT） were measured by standard biochemical assays. The relationship between miR-let-7b expression and disease parameters was assessed by Spearmans rank correlation test. Results PBC patients showed significantly lower expression of miR-let-7b in peripheral blood cells than healthy controls （P 〈 0.001）; moreover, the miR-let-7b expression level decreased in parallel to increases in disease severity （stage I 〉 Ⅱ / Ⅲ 〉 IV）. In PBC paitents, the miR-let-7b expression was significantly correlated with Mayo risk scores （r=-0.4930,P 〈 0.001）, IL-18 （r = -0.4643,P 〈 0.001） and ALP （r=-4119,P 〈0.001）, but not with TBIL or GGT. Conclusion Decreased expression of miR-let-7b may be associated with development and progression of PBC, and this miRNA may represent a novel target of improved diagnostic and preventive strategies for PBC.

关 键 词：原发性胆汁性肝硬化 miR-let-7b 自身免疫性疾病 

分 类 号：R575.2[医药卫生—消化系统]