文章摘要
李济民,朱 辉,徐 可,王 飞,杨 璐,叶泽康,谈楚楚,顾 倩,王 静,李春坚.氯吡格雷低反应冠心病患者血小板miRNA表达谱差异[J].南京医科大学学报,2021,(8):1178~1184
氯吡格雷低反应冠心病患者血小板miRNA表达谱差异
Differential expression profile of platelet miRNA in patients with coronary artery disease and clopidogrel low response
投稿时间:2021-03-23  
DOI:doi:10.7655/NYDXBNS20210811
中文关键词: 冠心病  氯吡格雷低反应性  血小板  微小RNA  表达谱
英文关键词: coronary artery disease  clopidogrel low response  platelet  miRNA  expression profile
基金项目:国家自然科学基金(81170181);江苏省医学重点人才(ZDRCA2016013)
作者单位
李济民 南京医科大学第一附属医院心脏科江苏 南京 210029阜阳市第五人民医院心血管内科二病区安徽 阜阳 236000 
朱 辉 南京医科大学第一附属医院心脏科江苏 南京 210029南京医科大学附属常州第二人民医院老年病科江苏 常州 213000 
徐 可 南京医科大学第一附属医院心脏科江苏 南京 210029 
王 飞 南京医科大学第一附属医院心脏科江苏 南京 210029 
杨 璐 南京医科大学第一附属医院心脏科江苏 南京 210029 
叶泽康 南京医科大学第一附属医院心脏科江苏 南京 210029 
谈楚楚 南京医科大学第一附属医院心脏科江苏 南京 210029 
顾 倩 南京医科大学第一附属医院心脏科江苏 南京 210029 
王 静 南京医科大学第一附属医院心脏科江苏 南京 210029 
李春坚 南京医科大学第一附属医院心脏科江苏 南京 210029 
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中文摘要:
      目的:探讨氯吡格雷低反应(clopidogrel low response,CLR)与正常反应的冠心病(coronary artery disease,CAD)患者血小板miRNA表达谱的差异。方法:连续入选78例接受氯吡格雷治疗(负荷剂量300 mg,维持剂量75 mg/d)至少5 d的冠心病患者,通过光学血小板聚集仪检测所有患者二磷酸腺苷诱导的血小板聚集率(platelet aggregation induced by adenosine diphosphate,PLADP),PLADP大于上四分位数的19例患者为CLR组,小于下四分位数的19例患者为对照组。提取所有入选患者纯化血小板中的总RNA,将上述两组患者的总RNA分别混为2个总RNA池,通过RNA变性电泳质检后,采用高通量测序筛选两组患者血小板miRNA的差异表达谱。通过靶基因预测软件TargetScan、miRanda、PITA和miRWalk对差异miRNA的功能进行预测。结果:两组患者临床基线资料无统计学意义。CLR组PLADP显著高于对照组(P < 0.000 1)。通过RNA变性电泳检测两组总RNA未见明显降解。高通量测序发现95种血小板miRNA表达上存在显著差异,其中显著性下调且差异倍数>2的拷贝数前20 位miRNA依次是hsa?miR?300、hsa?miR?151b、hsa?miR?1299等。通过至少2个靶基因预测软件印证8个miRNA(hsa?miR?188?5p、hsa?miR?6874?3p、hsa?miR?218?5p、hsa?miR?3150b?3p、hsa?miR?1288?3p、hsa?miR?1299、hsa?miR?6862?5p、hsa?miR?4421)对血小板聚集关键蛋白有调控作用。结论:CLR患者中存在血小板miRNA的显著下调,本研究筛选出8个对血小板聚集关键蛋白可能有调控作用的miRNA,可能成为个体化抗血小板治疗提供新的干预手段。
英文摘要:
      Objective:This study aims to detect the differential expression profile of platelet miRNAs(miRNA)in patients with coronary artery disease(CAD)and clopidogrel low response(CLR). Methods:A total of 78 CAD patients with clopidogrel treatment(loading dose 300 mg and maintenance dose 75 mg/d)at least 5 days were consecutively enrolled. Adenosine diphosphate(ADP)induced platelet aggregation(PLADP)was tested by light transmittance aggregation(LTA). Nineteen patients whose PLADP were at upper quartile were defined as CLR group,while another nineteen patients at lower quartile were selected as control. The total RNA of leukocyte depleted platelet(LDP)were extracted from each of the selected patients,and the extracted total RNA from the two groups were mixed into two RNA pools respectively. After two RNA pools were qualified by RNA denaturation electrophoresis,the differential expression profiles of platelet miRNAs were screened by high?throughput sequencing. The target gene predicting software including TargetScan,miRanda,PITA and miRWalk were adopted to explore the miRNAs that modulate the key protein in the process of platelet aggregation. Results:Baseline clinical characteristics of the two groups showed no significant difference. The PLADP level of the CLR group was significantly higher than that of the control group(P < 0.000 1). The total RNA pools of the two groups were detected by RNA denaturation electrophoresis and no significant degradation was found. 95 platelet miRNAs were differently expressed by high?throughput sequencing between the two groups,among which 20 miRNAs(hsa?miR?300,hsa?miR?151b,hsa?miR?1299,et al)were 2?fold down?regulated in CLR patients,and 8 miRNAs(hsa?miR?188?5p、hsa?miR?6874?3p、hsa?miR?218?5p、hsa?miR?3150b?3p、hsa?miR?1288?3p、hsa?miR?1299、hsa?miR?6862?5p、hsa?miR?4421)were identified by at least two target gene predicting software as having regulatory effects on key proteins associated with platelet aggregation. Conclusion:There is a significant downregulation of platelet miRNAs in CLR patients. We successfully screen 8 miRNAs that could modulate the key protein in the process of platelet aggregation,which is warrant to be investigated in future study.
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