抗结核药物肝损伤与无肝损伤患者化疗前血循环miRNA分子的差异性表达  

Differentially expressed microRNAs in plasma of pretreated patients with/without anti-tuberculosis drugs-induced hepatotoxicity

作　　者：叶长根[1,2] 孙水林[3] 白茹[1] 朱伟星[1] 陈彩萍[1] 谢平[1] 赵晖[1] 涂文娟[1] 高得勇[1] 刘亮明[1] 

机构地区：[1]上海交通大学附属第一人民医院松江分院感染科,上海市201600 [2]景德镇市第三人民医院消化内科,江西省景德镇市333000 [3]南昌大学第二附属医院感染科,江西省南昌市330000

出　　处：《世界华人消化杂志》2014年第3期415-422,共8页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;Nos.81070357;30660066;上海市松江区医学领先合作基金资助项目;No.2011LX02~~

摘　　要：目的:研究抗结核药物肝毒性(anti-tuberculosis drug-induced hepatotoxicity,ATDH)与非ATDH患者化疗前血浆差异性表达的miRNA分子,为ATDH易感者筛检提供新的生物学指标.方法:采用miRNA芯片检测ATDH及对照患者化疗前血浆标本.对存在差异表达趋势的25种miRNA分子,采用高通量实时荧光定量PCR进行分析验证.应用互联网上miRNA靶基因预测软件对表达上调的miRNA进行靶基因预测,并采用PANTHER tool查找靶蛋白GO功能分类.结果:与对照组相比,ATDH患者化疗前血浆中共检出7个差异性表达的miRNA分子,其中表达上调的miRNA有4个,包括miR-4284、miR-3620、miR-652-5p和miR-4800-5p;表达下调的miRNA有3个,包括miR-338-3p、miR-424-5p和miR-194-5p.结论:ATDH患者化疗前血浆内存在差异性表达的miRNA分子,其中表达上调的miRNA分子(特别是miR-4284)可能作为ATDH易感者筛检的生物学指标.AIM： To investigate differential expression profile of microRNAs （miRNAs） in plasma of pre- treated patients with/without anti-tuberculosis drug-induced hepatotoxicity （ATDH）. METHODS： Plasma samples were collected from patients with/without ATDH before anti- tuberculosis treatment and subjected to miRNA microarray analysis. Twenty-five miRNAs were tested using high-flux real-time quantitative PCR. The target genes of miRNAs were pre- dicted using the Internet software, and the GO functional classification of target proteins was analyzed using the PANTHER tool. RESU LTS： Compared with patients without ATDH, there were 7 miRNAs differentially ex- pressed in patients with ATDH before anti-tubercu- losis drug therapy, 4 of which were up-regulated, including miR-4284, miR-3620, miR-652-5p and miR-4800-Sp, and 3 down-regulated, including miR- 338-3p, miR-424-Sp and miR-194-Sp. CONCLUSION： There are differentially ex- pressed miRNAs in the circulation of patients with ATDH before anti-tuberculosis drug therapy, and the up-regulated miRNAs （esp. miR-4284） may be new biological markers for screening ATDH susceptible population.

关 键 词：抗结核药物 肝毒性 microRNA 血浆 差异性表达 

分 类 号：R595.3[医药卫生—内科学]