血清miRNA-370与颈动脉粥样硬化微栓子形成间的关系研究
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摘要
目的探讨颈动脉粥样硬化微栓子(MES)的形成与患者血清微小RNA-370(miR-370)表达水平间的关系。方法从心内超声科确诊的高血压合并颈动脉粥样硬化患者中筛选出不稳定性斑块患者135例,应用经颅彩色多普勒检查鉴定出MES阳性73例(MES阳性组)和MES阴性62例(MES阴性)。同时,选取60名健康者作为对照组。采用实时定量PCR技术检测所有研究对象血清miR-370的表达水平。结果 MES阳性和阴性组患者血清中miR-370的表达量均高于对照组,且MES阳性组更显著,差异均有统计学意义(P<0.01)。根据上调的中位倍数(3.05倍)分为miR-370高表达(>3.05倍,68例)和低表达(≤3.05倍,67例)。MES阳性组中miR-370高表达的患者显著高于MES阴性组(61.6%vs 37.1%,P<0.01)。Spearman相关性分析显示,血清miR-370表达水平与低密度脂蛋白、总胆固醇、甘油三酯及同型半光氨酸水平呈正相关(P<0.05或0.01)。结论血清miR-370表达水平与颈动脉粥样硬化MES的形成有关,或可作为分子标记物监测斑块的发生和发展。
Objective To investigate the relationship between serum miR-370 level and formation of carotid atherosclerosis micro embolus(MES). Methods A total of 135 cases with unstable plaque were selected from the patients diagnosed with hypertension complicated with carotid atherosclerosis by the Department of Intracardiac Ultrasound. There were 73 cases with MES positive(MES Positive Group) and 62 cases with MES negative(MES Negative Group) identified in transcranial color Doppler examination. At the same time, 60 healthy persons were selected as the Control Group. The MiR-370 expression in all serum samples was detected by using real-time PCR technique. Results The expression of miR-370 in MES Positive and Negative Group was higher than the Control Group, and the MES Positive Group showed a more significant increase, and the difference was statistically significant(P<0.01). According to the upregulated "multiples of the median"(3.05), it was divided into miR-370 high expression(>3.05, 68 cases) and miR-370 low expression(≤3.05, 67 cases). The number of patients with miR-370 high expression in MES Positive Group was greater than that in MES Negative Group(61.6% vs 37.1%, P<0.01).The Spearman correlation analysis showed that serum miR-370 level was positively correlated with LDL, total cholesterol,triglycerides and homophenine level(P<0.01). Conclusion Serum miR-370 level in patients with carotid atherosclerosis is significantly relevant to the formation of MES and may represent a novel biomarker for monitoring the occurrence and development of plaque.
Objective To investigate the relationship between serum miR-370 level and formation of carotid atherosclerosis micro embolus(MES). Methods A total of 135 cases with unstable plaque were selected from the patients diagnosed with hypertension complicated with carotid atherosclerosis by the Department of Intracardiac Ultrasound. There were 73 cases with MES positive(MES Positive Group) and 62 cases with MES negative(MES Negative Group) identified in transcranial color Doppler examination. At the same time, 60 healthy persons were selected as the Control Group. The MiR-370 expression in all serum samples was detected by using real-time PCR technique. Results The expression of miR-370 in MES Positive and Negative Group was higher than the Control Group, and the MES Positive Group showed a more significant increase, and the difference was statistically significant(P<0.01). According to the upregulated "multiples of the median"(3.05), it was divided into miR-370 high expression(>3.05, 68 cases) and miR-370 low expression(≤3.05, 67 cases). The number of patients with miR-370 high expression in MES Positive Group was greater than that in MES Negative Group(61.6% vs 37.1%, P<0.01).The Spearman correlation analysis showed that serum miR-370 level was positively correlated with LDL, total cholesterol,triglycerides and homophenine level(P<0.01). Conclusion Serum miR-370 level in patients with carotid atherosclerosis is significantly relevant to the formation of MES and may represent a novel biomarker for monitoring the occurrence and development of plaque.
引文
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[13]FARHAT N,THORIN-TRESCASES N,MAMARBACHIM,et al.Angiopoietin-like 2 promotes atherogenesis in mice[J].J Am Heart Assoc,2013,2(3):e201.
[14]BELLARY S,FAINT J M,ASSI L K,et al.Elevated serum free light chains predict cardiovascular events in type 2diabetes[J].Diabetes Care,2014,37(7):2028-2030.
[2]宫健,彭思存.颈动脉粥样硬化斑块超声特征与微栓子信号的临床研究[J].中国临床医学影像杂志,2005,16(7):371-372,375.
[3]TAO J,LI S F,XU M.The roles of microRNA in the diagnosis and therapy for cardiovascular diseases[J].Sheng Li Ke Xue Jin Zhan,2011,42(5):335-339.
[4]CHEN K C,LIAO Y C,HSICH I C,et al.OxLDL causes both epigenetic modification and signaling regulation on the microRNA-29b gene:novel mechanisms for cardiovascular diseases[J].J Mol Cell Cardiol,2012,52(3):587-595.
[5]GAO W,HE H W,WANG Z M,et al.Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease[J].Lipids Health Dis,2012,11:55.
[6]MITCHELL P S,PARKIN R K,KROH E M,et al.Circulating microRNAs as stable blood-based markers for cancer detection[J].Proc Natl Acad Sci USA,2008,105(30):10513-10518.
[7]巩向宇.多层螺旋CT在脑血管疾病中的诊断及应用[J].中外健康文摘,2012(40):212.
[8]刘鑫爱.微栓子监测在缺血性脑血管病中的临床应用与研究现状[J].医学综述,2011,17(17):2691-2694.
[9]ZHANG C,QU S,LI H,et al.Microembolic signals and carotid plaque characteristics in patients with asymptomatic carotid stenosis[J].Scand Cardiovasc J,2009,43(5):345-351.
[10]沈焱,白向东,马瑞莲,等.基质金属蛋白酶-9基因多态性与颈动脉粥样硬化微栓子形成的相关性研究[J].宁夏医学杂志,2013,35(3):207-210.
[11]RITTER M A,DITTRICH R,THOENISSEN N,et al.Prevalence and prognostic impact of microembolic signals in arterial sources of embolism.A systematic review of the literature[J].J Neurol,2008,255(7):953-961.
[12]OWENS G K,KUMAR M S,WAMHOFF B R.Molecular regulation of vascular smooth muscle cell differentiation in development and disease[J].Physiol Rev,2004,84(3):767-801.
[13]FARHAT N,THORIN-TRESCASES N,MAMARBACHIM,et al.Angiopoietin-like 2 promotes atherogenesis in mice[J].J Am Heart Assoc,2013,2(3):e201.
[14]BELLARY S,FAINT J M,ASSI L K,et al.Elevated serum free light chains predict cardiovascular events in type 2diabetes[J].Diabetes Care,2014,37(7):2028-2030.