血清微小核糖核酸-595在慢性乙型肝炎肝功能衰竭患者中的表达及其与疾病预后的关系  

The expression of circulating microRNA-595 in patients with hepatitis B virus-related liver failure and its relationship with disease prognosis

作　　者：王芃[1] 项晓刚[1] 莫瑞东[1] 赖荣陶[1] 王伟静[1] 刘昱含[1] 赵钢德[1] 郭斯敏[1] 俞红[1] 周惠娟[1] 蔡伟[1] 王晖[1] 韩艳[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9期545-549,共5页Chinese Journal of Infectious Diseases

基　　金：基金项目：国家科技部十二五重大专项基金资助项目（2012ZX10002004-003,2012ZX10002007-002-003）;国家自然科学基金项目资助（81071358,81171569）;上海市学科带头人计划（12XD1403600）

摘　　要：目的：研究 CHB 肝功能衰竭患者外周血 miRNA 的表达及其与疾病预后的关系。方法收集2011年8月至11月上海交通大学医学院附属瑞金医院感染科5例 CHB 肝功能衰竭患者和5名健康者的血清进行 Exiqon miRCURY LNATM miRNA 芯片检测。在此基础上另收集20例 CHB、20例CHB 后肝硬化、50例 CHB 肝功能衰竭患者和40名健康志愿者的血清，通过实时定量 PCR 法检测 miRNA-595相对表达量。组间均数比较采用 t 检验，相关性分析采用 Pearson 和 Spearman 相关分析。结果芯片微阵列分析发现，CHB 肝功能衰竭患者血清中有92个 miRNA 发生变化，以miRNA-595上调最为显著。实时定量 PCR 验证发现，CHB 肝功能衰竭患者 miRNA-595、miRNA-300、miRNA-122相对表达量分别为6．03（t＝3．134，P ＝0．003）、3．12（t＝7．221，P ＜0．01）、2．77（t ＝2．671， P ＝0．021），均明显高于健康对照组。CHB 肝功能衰竭患者血清 miRNA-595表达变化以及与疾病预后的相关性发现，CHB、CHB 后肝硬化、CHB 肝功能衰竭患者血清中 miRNA-595相对表达量分别为2．26（t＝3．780，P ＝0．001）、3．32（t＝6．111，P ＜0．01）、6．03（t＝3．134，P ＝0．003），均较对照组明显上升，且CHB 肝功能衰竭患者血清中 miRNA-595相对表达量较 CHB 患者升高2．66倍（t＝2．450，P ＝0．043）。按 PTA 分组发现，CHB 肝功能衰竭早期患者的血清 miRNA-595相对表达量明显升高。按 MELD 评分分组发现，MELD 评分≤30组患者血清 miRNA-595相对表达量与 MELD 评分呈正相关（r ＝0．673， P ＝0．004）。随访3个月发现，存活组（23例）在入院时的血清 miRNA-595相对表达量为11．08，死亡组（27例）为3．67，存活组明显高于死亡组（t ＝4．309，P ＝0．041）。结论CHB 肝功能衰竭患者血清中miRNA-595、miRNA-300和 miRNA-122均有所升高，其中早期患者血清中 miRNA-595升高最明显，可作为�Objective To measure the expression of circulating microRNA （miRNA）in patients with hepatitis B virus （HBV）-related liver failure and its relationship with disease prognosis.Methods The miRNA expressions in serum of 5 patients with HBV-related liver failure and 5 healthy control subjects were compared using Exiqon miRCURY LNATM miRNA microarray.The sera from 20 patients with chronic hepatitis B （CHB）,20 patients hepatitis B related cirrhosis,50 patients with HBV-related liver failure and 40 healthy persons in Ruijin Hospital were collected.The relative expression of miRNA-595 was measured using quantitative real-time polymerase chain reaction （PCR）.The relative expressions of miRNAs among groups were analyzed using student t test,the correlations were analyzed by Pearson and Spearman correlation.Results Microarray informed that 92 miRNAs changed significantly in patients with HBV-related liver failure,and miRNA-595 increased most significantly.The results of real-time PCR showed that the relative expressions of miRNA-595 ,miRNA-300 and miRNA-122 were 6.03 （t=3.134, P =0.003）,3.12 （t=7.221 ,P 〈0.01）and 2.77 （t=2.671 ,P =0.021）,which were higher compared to those in healthy control group.In the analysis of the relationship between miRNA-595 expression and disease prognosis in patients with HBV-related liver failure,the relative expressions of miRNA-595 in patients with CHB,hepatitis B related cirrhosis and HBV-related liver failure were 2.26 （t =3.780,P =0.001）,3.32 （t = 6.111 ,P 〈 0.01）and 6.03 （t = 3.134,P = 0.003）,respectively,which were all increased compared to that of the healthy control.The relative expression of miRNA-595 of patients with HBV-related liver failure was 2.66 times （t=2.450,P =0.043）higher than that of patients with CHB. When dividing patients according to prothrombin activity,miRNA-595 increased significantly in patients with early stage liver failure.When dividing patients according to model of end-stage liver disease （MELD） score,MELD scor

关 键 词：微小核糖核酸-595 血清 肝炎 乙型 肝功能衰竭 表达谱 

分 类 号：R512.62[医药卫生—内科学]