抗结核药物肝毒性对血浆miRNA分子表达的影响  

Effect of anti-tuberculosis drug-induced hepatotoxicity on plasma microRNA expression

作　　者：叶长根[1] 谢平[1] 刘亮明[1] 白茹[1] 陈彩萍[1] 朱伟星[1] 赵晖[1] 王迎迎[1] 汪妍妍 吴剑琴[1] 高得勇[1] 徐国荣[1] 夏利萍[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201600

出　　处：《上海交通大学学报（医学版）》2014年第2期154-160,164,共8页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金(81070357;30660066);上海市松江区医学领先合作项目(2011LX02)~~

摘　　要：目的探讨抗结核药物肝毒性(ATDH)对患者血浆中微RNA(miRNA)分子表达的影响。方法对3例活动性肺结核患者用药前和发生ATDH后的血浆标本进行miRNA芯片检测。对存在差异性表达的miRNA分子,采用Real Time-PCR进行验证。应用互联网miRNA靶基因预测软件对经证实存在差异性表达的miRNA进行靶基因预测,采用PANTHER蛋白分类系统查找靶蛋白基因本体(GO)功能分类。结果 ATDH发生后,血浆中共筛选出22个与用药前比较差异性表达的miRNA分子,表达上调和下调的miRNA各11个。Real Time-PCR验证结果显示:ATDH发生后,患者血浆中显著上调的miRNA有5个,分别为miR-378i、miR-125b-5p、miR-1224-5p、miR-194-5p和miR-34a-5p;下调的miRNA有3个,分别为miR-1260a、miR-338-3p和miR-4286。结论 ATDH发生患者血浆中存在与用药前比较差异性表达的miRNA分子,这些分子的存在可能与ATDH的发生有关。Objective To investigate the effect of anti-tuberculosis drug-induced hepatotoxicity （ATDH） on the expression of miRNA in patients＇ plasma. Methods The plasma from 3 patients with ATDH was collected and subjected to miRNA microarray analysis before anti-tuberculosis treatment and after liver injury during drug therapy. The differentially expressed miRNAs were verified using real-time quantitative PCR. The target genes of miRNAs were predicted by the Internet software, and the GO functional classification of target proteins were found by the PANTHER protein classification system. Results After ATDH had occurred, the microarray screened 22 differentially expressed miRNAs compared to those of pretreatment, among which II were up-regulated, and 11 were down-regulated. Real-time quantitative PCR results showed that after ATDH there were 5 up-regulated miRNAs, namely miR-378i, miR-125b-Sp, miR-1224-Sp, miR-194-Sp and miR-34a-Sp, and 3 down-regulated miRNAs, namely miR-1260a, miR-338-3p and miR-4286. Conclusion There are differentially expressed miRNAs in the plasma of patients after ATDH, and these miRNAs may be related to the incidence of ATDH.

关 键 词：抗结核药物 肝毒性 微RNA 血浆 差异性表达 

分 类 号：R575[医药卫生—消化系统]