血清微小核糖核酸-122在慢性乙型肝炎肝功能衰竭患者中的表达及其与疾病严重程度的关系  

The expression of serum microRNA-122 in patients with chronic hepatitis B virus-related liver failure and its relationship with severity of disease

作　　者：王伟静[1] 项晓刚[1] 赵钢德[1] 赖荣陶[1] 王芃[1] 莫瑞东[1] 郭斯敏[1] 周惠娟[1] 刘芸野[1] 王晖[1] 谢青[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》2014年第5期269-273,共5页Chinese Journal of Infectious Diseases

基　　金：国家科技部十二五重大专项基金资助项目（2012ZX10002004、2012ZX10002007、2012ZX09303-001）;国家自然科学基金资助项目（81071358）

摘　　要：目的 探讨CHB肝功能衰竭患者外周血循环miRNA的表达及其与疾病严重程度的关系.方法 选择2011年8月至2011年11月在上海交通大学医学院附属瑞金医院就诊的CHB肝功能衰竭患者5例及健康体检者5名,进行血清Exiqon LNA miRNA芯片分析.另选2010年8月至2012年3月就诊的急性乙型肝炎10例、CHB 22例、乙型肝炎肝硬化12例、CHB肝功能衰竭58例,健康体检者23名,实时定量PCR检测血清miRNA-122相对表达量.且对不同PTA程度、不同终末期肝病模型（MELD）评分的CHB肝功能衰竭患者miRNA-122相对表达量进行比较.相关性分析采用Pearson和Spearman相关分析,生存分析采用Kaplan-Meier分析.结果 芯片分析结果显示,CHB肝功能衰竭患者血清有148个miRNA发生显著变化,其中3个上调,为miRNA-122、miRNA-595和miRNA-300,145个下调.实时定量PCR结果显示,与健康对照者相比,各组患者血清miRNA-122相对表达量均有不同程度的升高.CHB肝功能衰竭组miRNA-122相对表达量最高,且30％＜PTA≤40％患者血清miRNA-122相对表达量是20％ ＜PTA≤30％患者的1.8倍,是PTA≤20％患者的2.3倍.MELD评分≤30时,血清miRNA-122表达水平随肝功能衰竭程度加重而升高,且与MELD评分呈正相关（r=0.521,P＜0.01）;而当MELD评分＞30时,血清miRNA-122表达量升高反而不明显.动态观察发现CHB肝功能衰竭患者血清miRNA-122表达量随病情好转而下降.结论 早期CHB肝功能衰竭患者血清miRNA-122相对表达量明显上升,可作为监测疾病严重程度的血清标志物.Objective To measure the expression of circulating microRNA （miRNA） in patients with chronic hepatitis B virus （HBV）-related liver failure and its relationship with severity of disease.Methods The miRNA expressions in serum from 5 patients with chronic HBV-related liver failure and 5 healthy control subjects who visited Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine from August 2011 to November 2011 were measured using Exiqon LNA microarray.Another 125 serum samples from 10 patients with acute hepatitis B,22 chronic hepatitis B,12 hepatitis B related cirrhosis,58 chronic HBV-related liver failure and 23 healthy control subjects from August 2010 to March 2012 were collected.Quantitative real-time polymerase chain reaction （PCR） was used to measure the relative expression levels of miRNA-122 in serum.The correlation analysis was analyzed by Pearson and Spearman correlation and the survival was analyzed by Kaplan-Meier method.Results Microarray indicated that 148 miRNAs changed significantly in the serum of patients with chronic HBV-related liver failure.Among them,3 were up-regulated,including miRNA-122,miRNA-595 and miRNA-300,while 145 were down-regulated.The results of PCR indicated that the expression level of miRNA-122 increased significantly in patients compared to healthy control subjects.The relative expression level of miRNA-122 was highest in patients with chronic HBV-related liver failure.The serum expression in patients with 30 % 〈prothrombin activity （PTA）≤40% was 1.8 times higher than those with 20%〈PTA≤30%,and 2.3 times higher than those with PTA≤20%.Moreover,the expression of miRNA-122 increased along with the severity of liver failure,and was positively correlated with model for end-stage liver disease （MELD） score （r=0.521,P〈0.01） when MELD score was under 30.However,the expression of serum miRNA-122 had no significant change when MELD score 〉 30.Dynamic observation of miRNA expression showed that the serum level of miRNA in patie

关 键 词：微小核糖核酸 血清 肝炎 乙型 慢性 肝功能衰竭 聚合酶链反应 芯片分析技术 

分 类 号：R512.62[医药卫生—内科学]