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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 antituberculosis drug hepatotoxicity (ATDH) on the expression of microRNA (miRNA) in plasma of patients. Methods Plasma samples from 3 patients with active pulmonary tuberculosis before and after ATDH were detected by miRNA microarray. Real-time PCR was used to validate the differentially expressed miRNA molecules. The Internet miRNA target gene prediction software was used to predict target genes of miRNAs that were differentially expressed, and the PANTHER protein classification system was used to search the functional classification of the target protein gene body (GO). Results After ATDH, 22 miRNAs that were differentially expressed before treatment were screened out, and 11 miRNAs were up-regulated and down-regulated, respectively. Real Time-PCR results showed that there were 5 miRNAs significantly up-regulated in the plasma of patients after ATDH, which were miR-378i, miR-125b-5p, miR-1224-5p, miR-194-5p and miR-34a -5p; down-regulated miRNA has 3, respectively, miR-1260a, miR-338-3p and miR-4286. Conclusions The presence of miRNAs in plasma of patients with ATDH, which were differentially expressed before administration, may be related to the occurrence of ATDH.