细胞Toll样受体4／微小核糖核酸-181a在慢性乙型肝炎肝纤维化进程中的动态表达及临床意义  

Dynamic expressions and clinical significance of toil-like receptor 4/microRNA-181a in the pathogenesis of hepatic fibrosis in patients with chronic hepatitis B

作　　者：陈靖[1] 郑琦[1] 曾达武[1] 陈薇[1] 朱月永[1] Chen Jing;Zheng Qi;Zeng Dawu;Chen Wei;Zhu Yueyong(Liver Diseases Center,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院肝病中心,福州350005

出　　处：《中华传染病杂志》2018年第8期466-472,共7页Chinese Journal of Infectious Diseases

基　　金：国家科技重大专项项目（2017ZX10202201-001-006）;福建省自然科学基金项目（2018J01174）;福建省卫生系统中青年骨干人才培养项目（2015-ZON-JC-25）

摘　　要：目的探讨TLR4／微小核糖核酸（microRNA，miRNA）-181a在CHB肝纤维化进程中的作用及临床意义。方法CHB患者经肝活组织检查进行肝纤维化分期（s）；实时PCR法检测肝组织、血清miRNA-181a以及肝组织TLR4mRNA表达；蛋白质印迹法检测肝组织TLR4蛋白；计算基于4因子的纤维化指数（fibrosisindexbasedonthe4factors，FIB-4）及天冬氨酸转氨酶与血小板比值指数（aspartateaminotransferase-to-plateletratioindex，APRI）进行非侵袭性肝纤维化诊断；对数据采用单因素方差分析、Mann-WhitneyU检验、Spearman相关分析及受试者工作特征曲线（receiveroperationcharacteristiccurve，ROC曲线）分析。结果40例CHB患者，sO期（7例）、S1期（6例）、82期（14例）、s3期（7例）和s4期（6例）血清miRNA-181a表达水平（2。“‘值）分别为1．oO±0．00、0．68_4-0．08、1．60±0．43、2．32±0．40和1．81±0．22，总体呈上升趋势（F-207．242，P=0．000），与肝纤维化严重程度呈正相关（r=0．754，P〈0．01）；随肝纤维化分期加重，肝组织miRNA-181a、TLR4mRNA及TLR4蛋白表达总体呈上升趋势（F值分别为207．242，110．390和57．030，均P〈0．01），肝组织miRNA-181a与TLR4蛋白表达及肝纤维化严重程度均呈正相关（r值分别为0．673和0．911，均P〈O．01）。严重肝纤维化（S3～84）组APRI与非严重肝纤维化（SO～s2）组差异无统计学意义（Z=-1．401，P〉0．05）。血清miRNA-181a表达评估严重肝纤维化（S3～s4）优于FI睁4（ROC曲线下面积：0．887比0．695；准确度：85．0％比60．0％）。结论miRNA-181a可能参与TLR4信号通路的调控而影响CHB患者肝纤维化进程，有望成为防治肝纤维化新的“靶点”及非侵袭性评估肝纤维化的血清指标。Objective T0 exPlore the dynamic expressions and clinical significance of toll-like receptor 4 （TLR4）/microRNA （miRNA）-181a in the pathogenesis of hepatic fibrosis （HF） in patients with chronic hepatitis B （CHB）. Methods CHB patients underwent liver biopsy for fibrosis staging HF （S）. Real-time polymerase chain reaction （PCR） was used to detect the expressions of miRNA-181a in both serum and liver tissue and the expression of TLR4 mRNA in liver tissue. Western blot was used to detect the expression of TLR4 protein in liver tissue. The fibrosis-4 （FI13-4） index and aspartate aminotransferase-to-platelet ratio index （APRI） were calculated for noninvasive evaluation of fibrosis staging. One-way ANOVA, Mann-Whitney U test, spearman correlation analysis and receiver operating characteristic （ROC） curve were used for statistical analysis. Results Forty CHB patients were included in this study, including, 7 with SO, 6 with S1, 14 with S2, 7 with S3 and 6 with S4. Serum levesl of miRNA-181a （2 -CT） inpaitentswithS0-4 were 1.004±0.00, 0.68±0.08, 1.60±0.43, 2.32±0.40, and 1.81±0.22, respectively, showing an overall upward trend （F=207. 242, P〈 0.01） and a positive correlation with the severity of HF （r= 0. 754, P〈 0. 01）. The expressions of miRNA-181a, TLR4 mRNA and TLR4 protein in liver tissues showed an overall increasing trend from SO to S4 （F=207. 242, 110. 390 and 57. 030, respectively, all P〈0.01）. The expression of miRNA-181a in liver tissue showed a positive correlation with both the expression of TLR4 protein in liver tissue and the severity of HF （r= 0. 673 and 0. 911, respectively, both P% 0. 01）. There was no significant difference of APRI scores between the severe （S3-4） and non-severe （S0-2） HF groups （Z=-1. 401, P〈0.05）. The serum level of miRNA-181a was superior to FIB-4 index for evaluation of the severe HF （S3-4）, with areas under the ROC curve （AUROC） of 0. 887 and 0. 695, respectively, and accuracy of 85. 0% and 60.

关 键 词：肝炎 乙型 慢性 肝硬化 TOLL样受体4 微小RNA-181a 

分 类 号：R512.62[医药卫生—内科学]