乙型肝炎患者外周血单个核细胞中微小RNA的表达变化  

The expression of microRNAs in the peripheral blood mononuclear cells of the patients with hepatitis B virus infection

作　　者：王琳[1] 谢青[1] 龚邦东[1] 安宝燕[1] 徐玉敏[1] 蔡伟[1] 王晖[1] 周惠娟[1] 郭斯敏[1] 俞红[1] 郭清[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025

出　　处：《中华传染病杂志》2010年第8期473-479,共7页Chinese Journal of Infectious Diseases

基　　金：国家科技部十一五重大传染病专项（2008ZX10002-005、2008ZX10002007、2008ZX09312-007）;国家自然科学基金项目（30872252）;上海市科委基础研究重点项目（08JC1415300）

摘　　要：目的 探讨乙型肝炎患者外周血单个核细胞（PBMC）中微小RNA（miRNA）和细胞因子的变化及其与炎性反应的相互关系.方法 收集健康对照者17例,急性乙型肝炎发作期、病毒清除期和恢复期患者各20例,慢性乙型肝炎轻度、中度和重度患者各20例和乙型肝炎后肝硬化患者20例.分离PBMC,采用反转录-荧光定量PCR方法检测miRNA146、miRNA155、miRNA181、IFN-α、IFN-β、IFN诱导基因54（ISG54）、IFN调节因子5（IRF5）的表达.多组间比较采用单因素方差分析.结果 急性乙型肝炎患者PBMC中miRNA155的表达水平在急性发作期（2.386±1.835）较高,明显高于健康对照组（1.498±1.276）,差异有统计学意义（F=1.137,P=0.045）,随疾病进入发作期、病毒清除期（1.633±2.291）、恢复期（0.642±0.836）,其表达逐渐降低（F=2.122,P=0.022）.同时IFN-α、IFN-β随急性发作期（7.059±9.594、4.767±6.725）、病毒清除期（2.216±2.148、1.750±1.403）和恢复期（0.642±0.836、1.201±0.779）其表达也逐渐降低（F=1.880,P=0.038;F=1.835,P=0.048）.相关性分析发现,miRNA155与IFN-α、IFN-β均具有良好的正相关性（r=0.483,P=0.004;r=0.660,P=0.0002）.在急性HBV感染患者中,miRNA155的表达与ALT、Tbil均呈正相关（r=0.342,P=0.006;r=0.322,P=0.011）,但与血清HBV DNA载量无相关性.miRNA181在HBV感染者PBMC中的表达,除急性乙型肝炎恢复期（1.873±0.998）外,均高于健康对照组（1.307±0.935）（F=2.072,P=0.045）,但HBV感染各组间差异无统计学意义.miRNA146的表达水平变化不明显.结论 在HBV感染过程中,miRNAs参与了宿主的抗HBV免疫反应,并与细胞因子表达相关.Objective To investigate the expressions of microRNAs （miRNA） and cytokines in the peripheral blood mononuclear cells （PBMCs） of patients with hepatitis B virus （HBV） infection and analyze their relationship with inflammation. Methods PBMCs were collected from acute hapatitis B （AHB） patients of 3 groups, including acute episode, virus clearance, recover period, and chronic hepatitis B （CHB） of mild, medium, severe type, and HBV-related liver cirrhosis. Each group included 20 patients, and 17 healthy donors were as control. Reverse transcription-polymerase chain reaction was used to measure miRNA146, miRNA155, miRNA181, interferon （IFN）-α, IFN-β,interferon induced gene 54 （ISG54） and interferon regulate factor 5 （IRF5）. Comparisons among groups were done by one factor analysis of variance. Results The expression of miRNA155 was high in acute episode of AHB （2. 386± 1. 835）, and higher than healthy control （1. 498± 1. 276） （F=1. 137,P-=0. 045）, while reduced in acute episode, virus clearance （1. 633±2. 291）, and recover period （0. 642±0. 836） （F=2. 122,P=0. 022）. The expressions of IFN-α and IFN-β in AHB reduced in acute episode, virus clearance and recover period （ F = 1. 880, P = 0. 038 ; F= 1. 835, P = 0. 048）.The expression of miRNA155 in AHB is closely correlated with IFN-α and IFN-β （r = 0. 483, P=0. 004; r= 0. 660, P= 0. 0002, respectively）. In addition, in HBV infectious patients, the expression of miRNA155 was correlated with alanine transarninase （ALT）, serum bilirubin （TBil） （r=0. 342,P=0. 006; r=0. 322, P= 0. 011, respectively）, but not with HBV DNA load. Compared with healthy control （1. 307＋ 0. 935）, miRNA181 was higher in patients with HBV infection （F= 2. 072, P=0. 045） except AHB in recover period （1. 873±0. 998）. There was no statistical difference in the miRNA146 expression between various groups. Conclusions The exprossion of miRNAs might be involved in the host anti-HBV immune response during H

关 键 词：肝炎病毒 乙型 做RNAs 细胞因子类 炎症 基因表达 单核细胞 肝炎 乙型 

分 类 号：R686[医药卫生—骨科学]