抗结核药物肝毒性对血浆miRNA分子表达的影响-论文.pdf

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1、上海交通大学学报(医学版)·154·JournalofShanghaiJiaoTongUniversity(MedicalScience)[文章编号]1674—8115(2014)02—0154—07·论著·抗结核药物肝毒性对血浆miRNA分子表达的影响叶长根，谢平，刘亮明，白茹，陈彩萍。朱伟星。赵晖，王迎迎，汪妍妍，吴剑琴，高得勇，徐国荣，夏利萍(上海交通大学附属第一人民医院松江分院感染科，上海201600)[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

2、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RealTime—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，表达上凋和下调的miRNA各11个。RealTime-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

3、为miR一378i、miR—l25b-5P、miR一1224—5P、miR一194—5P和miR一34a一5P；下调的miRNA有3个，分别为miR一1260a、miR一338—3P和miR一4286。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。[关键词]抗结核药物；肝毒性；微RNA；血浆；差异性表达[DOI]10．3969／j．issn．1674—8115．2014．02．006[中图分类号]Q78[文献标志码]AEffectofanti-

4、tuberculosisdrug-inducedhepat0t0xicityonplasmamicroRNAexpressionYEChang—gen，XIEPing，LIULiang—ming，BAIRu，CHENCai—ping，ZHUWei—xing，ZHAOHui，WANGYing—ying，WANGYan—yan，WUJian—qin，GAODe—yong，XUGuo—rong，XIALi—ping(DepartmentofInfectiousDiseases，SongjiangHospitalA

5、ffiliatedtotheFirstPeoplesHospital，ShanghaiJiaoTongUniversity，Shanghai201600，China)[Abstract】ObjectiveToinvestigatetheefectofanti—tuberculosisdrug—inducedhepatotoxicityfATDH)ontheexpressionofmiRNAinpatientsplasma．MethodsTheplasmafrom3patientswithATDHwascol

6、lectedandsubjectedtomiRNAmicroarrayanalysisbeforeanti—tuberculosistreatmentandafterliverinjuryduringdrugtherapy．ThediferentiallyexpressedmiRNAswereverifiedusingreal—timequantitativePCR．ThetargetgenesofmiRNAswerepredictedbytheInternetsoftware，andtheGOfuncti

7、onalclassificationoftargetproteinswerefoundbythePANTHERproteinclassificationsystem．ResultsAfterATDHhadoccurred，themicroarrayscreened22diferentiallyexpressedmiRNAscomparedtothoseofpretreatment，amongwhich11wereup—regulated，and11weredown—regulated．Real—timequ

8、antitativePCRresultsshowedthatafterATDHtherewere5up—regulatedmiRNAs，namelymiR一378i，miR一125b一5p，miR一1224—5p，miR一194—5pandmiR一34a一5P，and3down—regulatedmiRNAs，namelymiR一1260a，miR一338—3PandmiR一4286．ConclusionTher