颅内动脉支架成形术后再狭窄患者血清miRNA-210,miRNA-126水平检测的临床应用价值
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摘要
目的研究血清miRNA-210,miRNA-126表达在颅内动脉支架成形术后再狭窄中的临床应用价值。方法收集113例在延安大学咸阳医院接受颅内动脉支架成形术治疗的颅内动脉狭窄患者(再狭窄组23例,无狭窄组90例)及25例体检健康者(对照组)的血清及临床资料,采用实时逆转录-聚合酶链反应(RT-PCR)技术检测血清miRNA-210和miRNA-126的表达,比较分析其在各组中的变化。应用颈动脉超声检查评价颅内动脉支架成形术后再狭窄的发生。采用受试者工作特征曲线(ROC曲线)评价血清miRNA-210和miRNA-126的临床意义。结果血清miRNA-210和miRNA-126在对照组、无狭窄组和再狭窄组中的表达分别为0.25±0.07,0.53±0.16,0.93±0.23和0.97±0.27,0.67±0.19,0.23±0.09。与对照组比较,血清miRNA-210在再狭窄组和无狭窄组的表达明显增高,而miRNA-126表达则显著降低,差异均有统计学意义;与无狭窄组比较,再狭窄组miRNA-210表达水平明显增高,而miRNA-126表达则显著降低,其差异均有统计学意义(F=125.9,116.7,P=0.000)。颈动脉超声检查显示,颈内动脉内径(PD)和颈内动脉收缩期峰值流速(PSV)分别在对照组、无狭窄组和再狭窄组中的检查结果为5.51±0.72,4.70±0.63,3.07±0.52 mm和71.27±19.26,93.90±27.38,185.72±75.17cm/s。与对照组比较,再狭窄组和无狭窄组的PSV均显著增高,而PD则显著降低,其差异均有统计学意义。再狭窄组的PD与无狭窄组比较显著减小,而PSV则显著增快,其差异均有统计学意义(F=38.96,99.75,P=0.000)。miRNA-210和miRNA-126在再狭窄组的表达具有负相关性(r=-0.859,P<0.01),且分别与PD和PSV具有相关性(r=0.868,-0.852,P<0.01),(r=-0.897,0.876,P<0.01)。ROC曲线分析显示血清miRNA-210和miRNA-126水平的AUC分别为0.839(95%CI:0.755~0.942,P<0.01)和0.857(95%CI:0.749~0.966,P<0.01)。结论血清miRNA-210和miRNA-126水平检测可用于颅内动脉支架成形术后再狭窄的诊断以及预测,并可能成为该疾病的基因检测指标。
Objective To study the clinical value of expression of miRNA-210 and miRNA-126 in serum in the diagnosis of intracranial artery restenosis after stent angioplasty.Methods The serumal and clinical data of 113 cases of patients with intracranial artery stenosis(23 cases in the restenosis group,90 cases in the non-stenosis group)and 25 cases of healthy persons(control group)were collected at Xianyang Hospital of Yan'an University.The relative expression of miRNA-210 and miRNA-126 in serum was detected by qPCR technique,and compared and analyzed in the groups.Carotid artery ultrasonography was used evaluating occurrence of restenosis after intracranial artery stenting.The clinical significance of serum miRNA-210 and miRNA-126 was assessed via the receiver operating characteristic curve(ROC curve).Results The serumal expression of miRNA-210 and miRNA-126 in the control group,the non stenosis group and the restenosis group was 0.25±0.07,0.53±0.16,0.93±0.23 and 0.97±0.27,0.67±0.19,0.23±0.09,respectively.Compared with in the control group,the serumal expression of miRNA-210 in the restenosis group and the non-stenosis group increased significantly,while the miRNA-126 expression level decreased significantly,and the differences were statistically significant.In the restenosis group,miRNA-210 was significantly higher,but miRNA-126 decreased significantly(F=125.9,116.7,P=0.000),and these differences were statistically significant.According to carotid artery ultrasonography,the carotid artery diameter(PD)and its peak systolic velocity(PSV),repectively,in the control group,the stenosis group and the restenosisgroup were 5.51±0.72,4.70±0.63,3.07±0.52 mm and 71.27±19.26,93.90±27.38,185.72±75.17 cm/s,indicating that these facts of a decreased PD and increase PSV were noticed in the restenosis and the non-stenosis groups relatively to those in the control group,and that these were observed in the restenosis group compared with those in the non-stenosis group(F=38.96,99.75,P=0.000).In addition,an inverse relationship was described between the expression of miRNA-210 and miRNA-126 in the restenosis group(r=-0.859,P<0.01),and they were also clarified to be correlated with PD and PSV(r=0.868,-0.852,P<0.01 and r=-0.897,0.876,P<0.01),respectively.ROC curve analysis showed that AUC of miRNA-210 was 0.839(95%CI:0.755~0.942,P<0.01),and of miRNA-126 was 0.857(95%CI:0.749~0.966,P<0.01).Conclusion Detection of serumal miRNA-210 and miRNA-126 can be used for the diagnosis and prediagnosis of restenosis after intracranial artery stenting.They may be served as a marker of gene detection in the disease.
Objective To study the clinical value of expression of miRNA-210 and miRNA-126 in serum in the diagnosis of intracranial artery restenosis after stent angioplasty.Methods The serumal and clinical data of 113 cases of patients with intracranial artery stenosis(23 cases in the restenosis group,90 cases in the non-stenosis group)and 25 cases of healthy persons(control group)were collected at Xianyang Hospital of Yan'an University.The relative expression of miRNA-210 and miRNA-126 in serum was detected by qPCR technique,and compared and analyzed in the groups.Carotid artery ultrasonography was used evaluating occurrence of restenosis after intracranial artery stenting.The clinical significance of serum miRNA-210 and miRNA-126 was assessed via the receiver operating characteristic curve(ROC curve).Results The serumal expression of miRNA-210 and miRNA-126 in the control group,the non stenosis group and the restenosis group was 0.25±0.07,0.53±0.16,0.93±0.23 and 0.97±0.27,0.67±0.19,0.23±0.09,respectively.Compared with in the control group,the serumal expression of miRNA-210 in the restenosis group and the non-stenosis group increased significantly,while the miRNA-126 expression level decreased significantly,and the differences were statistically significant.In the restenosis group,miRNA-210 was significantly higher,but miRNA-126 decreased significantly(F=125.9,116.7,P=0.000),and these differences were statistically significant.According to carotid artery ultrasonography,the carotid artery diameter(PD)and its peak systolic velocity(PSV),repectively,in the control group,the stenosis group and the restenosisgroup were 5.51±0.72,4.70±0.63,3.07±0.52 mm and 71.27±19.26,93.90±27.38,185.72±75.17 cm/s,indicating that these facts of a decreased PD and increase PSV were noticed in the restenosis and the non-stenosis groups relatively to those in the control group,and that these were observed in the restenosis group compared with those in the non-stenosis group(F=38.96,99.75,P=0.000).In addition,an inverse relationship was described between the expression of miRNA-210 and miRNA-126 in the restenosis group(r=-0.859,P<0.01),and they were also clarified to be correlated with PD and PSV(r=0.868,-0.852,P<0.01 and r=-0.897,0.876,P<0.01),respectively.ROC curve analysis showed that AUC of miRNA-210 was 0.839(95%CI:0.755~0.942,P<0.01),and of miRNA-126 was 0.857(95%CI:0.749~0.966,P<0.01).Conclusion Detection of serumal miRNA-210 and miRNA-126 can be used for the diagnosis and prediagnosis of restenosis after intracranial artery stenting.They may be served as a marker of gene detection in the disease.
引文
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[12]唐苏铭,周晓航,李黎明,等.无镍不锈钢金属支架材料对血管内皮细胞凋亡的诱导机制[J].中国医科大学学报,2014,43(6):481-484.Tang SM,Zhou XH,Li LM,et al.Mechanisms of nickel free stainless steel indused apoptosis in vascular endothelial cells[J].Journal of China Medical University,2014,43(6):481-484.
[13]Xiang Y,Guo J,Peng E,et al.Association of miR-21,miR-126and miR-605gene polymorphisms with ischemic stroke risk[J].Oncotarget,2017,8(56):95755-95763.
[14]Jansen F,Stumpf T,Proehsting S,et al.Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6[J].J Mol Cell Cardiol,2017,104:43-52.
[15]Izuhara M,Kuwabara Y,Saito N,et al.Prevention of neointimal formation using miRNA-126containing nanoparticle-conjugated stents in a rabbit model[J].PLoS One,2017,12(3):e0172798.
[16]杨洁,王力力,凌晨,等.经颅多普勒超声联合经颅彩色多普勒超声评价基底动脉狭窄支架置入疗效及再狭窄因素的分析[J].中国脑血管病杂志,2016,13(4):169-173.Yang J,Wang LL,Ling C,et al.Evaluation of transcranial doppler combined with transcranial color coded sonography for basilar artery stent and followup study[J].Chinese Journal of Cerebrovascular Diseases,2016,13(4):169-173.
[2]肖小平,张熊,秦光明.食管癌和良性食管疾病患者血浆miRNA-21和miRNA-143检测的临床应用研究[J].现代检验医学杂志,2017,32(4):72-75,139.Xiao XP,Zhang X,Qin GM.Clinical research of detecting plasma miRNA-21and miRNA-143in identifying early esophageal cancer and benign esophageal diseases[J].Journal of Modern Laboratory Medicine,2017,32(4):72-75,139.
[3]张家康,王枭雄,陈鑫,等.急性缺血性脑卒中中循环miRNA的相关研究进展[J].卒中与神经疾病,2016,23(3):213-215.Zhang JK,Wang XX,Chen X,et al.Research progress of circulating miRNA in acute ischemic stroke[J].Stroke and Nervous Disease,2016,23(3):213-215.
[4]陶永,霍颖超,符晓艳,等.腔隙性脑梗死患者颅内动脉狭窄与脑白质病变发生的关系[J].中华解剖与临床杂志,2016,21(5):391-396.Tao Y,Huo YC,Fu XY,et al.The relationship between intracranial artery stenosis and white matter lesions in patients with lacunar infarcts[J].Chinese Journal of Anatomy and Clinical,2016,21(5):391-396.
[5]陈茹,张念军,赵敏,等.支架与药物治疗症状性颅内动脉狭窄远期疗效对比[J].介入放射学杂志,2016,25(2):97-101.Chen R,Zhang NJ,Zhao M,et al.Stenting and drug therapy for symptomatic intracranial artery stenosis:comparison of long-term efficacy[J].Journal of Interventional Radiology,2016,25(2):97-101.
[6]Katano H,Nishikawa Y,Yamada H,et al.Calcification in original plaque and restenosis following carotid artery stenting[J].Surg Neurol Int,2017,8(1):279.
[7]Page S,Munsell A,Al-Ahmad AJ.Cerebral hypoxia/ischemia selectively disrupts tight junctions complexes in stem cell-derived human brain microvascular endothelial cells[J].Fluids Barriers CNS,2016,13(1):16.
[8]Yang Z,Zhong L,Zhong S,et al.Hypoxia induces microglia autophagy and neural inflammation injury in focal cerebral ischemia model[J].Exp Mol Pathol,2015,98(2):219-224.
[9]Shen J,Zhu Y,Huang K,et al.Buyang huanwu decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells[J].BMC Complement Altern Med,2016,16:154.
[10]魏广和,蔺跃栋,苏强,等.冠状动脉支架内再狭窄相关miRNA的表达谱分析和意义[J].中国动脉硬化杂志,2017,25(8):800-806.Wei GH,Lin YD,Su Q,et al.MiRNA profiling and significance in coronary in-stent restenosis[J].Chinese Journal of Arteriosclerosis,2017,25(8):800-806.
[11]Wang J,Zhang Y,Xu F.Function and mechanism of microRNA-210in acute cerebral infarction[J].Exp Ther Med,2018,15(2):1263-1268.
[12]唐苏铭,周晓航,李黎明,等.无镍不锈钢金属支架材料对血管内皮细胞凋亡的诱导机制[J].中国医科大学学报,2014,43(6):481-484.Tang SM,Zhou XH,Li LM,et al.Mechanisms of nickel free stainless steel indused apoptosis in vascular endothelial cells[J].Journal of China Medical University,2014,43(6):481-484.
[13]Xiang Y,Guo J,Peng E,et al.Association of miR-21,miR-126and miR-605gene polymorphisms with ischemic stroke risk[J].Oncotarget,2017,8(56):95755-95763.
[14]Jansen F,Stumpf T,Proehsting S,et al.Intercellular transfer of miR-126-3p by endothelial microparticles reduces vascular smooth muscle cell proliferation and limits neointima formation by inhibiting LRP6[J].J Mol Cell Cardiol,2017,104:43-52.
[15]Izuhara M,Kuwabara Y,Saito N,et al.Prevention of neointimal formation using miRNA-126containing nanoparticle-conjugated stents in a rabbit model[J].PLoS One,2017,12(3):e0172798.
[16]杨洁,王力力,凌晨,等.经颅多普勒超声联合经颅彩色多普勒超声评价基底动脉狭窄支架置入疗效及再狭窄因素的分析[J].中国脑血管病杂志,2016,13(4):169-173.Yang J,Wang LL,Ling C,et al.Evaluation of transcranial doppler combined with transcranial color coded sonography for basilar artery stent and followup study[J].Chinese Journal of Cerebrovascular Diseases,2016,13(4):169-173.