何诺;谢林森;董丽;任江龙;

• 1:郑州大学附属郑州中心医院

摘要(Abstract)：

目的探讨血清小而密低密度脂蛋白胆固醇(sdLDL)、微小RNA-424(miR-424)、胰岛素样生长因子-1(IGF-1)表达与脑梗死溶栓治疗效果的关联性及其预测价值。方法选取2018-03—2020-02郑州大学附属郑州中心医院治疗的脑梗死患者129例,比较不同脑梗死面积、斑块性质、溶栓效果及预后患者血清sdLDL、miR-424、IGF-1表达水平,采用受试者工作特征曲线(ROC)及ROC下面积(AUC)分析sdLDL、miR-424、IGF-1预测脑梗死预后的截断值、敏感度、特异度,采用Pearson分析预后不良患者sdLDL、miR-424、IGF-1的关联性。结果 miR-424、IGF-1水平比较,大面积脑梗死<中面积脑梗死<小面积脑梗死;sdLDL水平比较,大面积脑梗死>中面积脑梗死>小面积脑梗死(P<0.05)。不稳定斑块脑梗死患者miR-424、IGF-1水平低于稳定斑块患者,sdLDL表达水平高于稳定斑块患者(P<0.05)。疗效良好者miR-424、IGF-1水平高于疗效不佳者,sdLDL水平低于疗效不佳者(P<0.05)。预后良好者miR-424、IGF-1水平高于预后不良者,sdLDL水平低于预后不良者(P<0.05)。预测脑梗死预后不良的AUC、截断值:sdLDL分别为0.787、>2.38 mmol/L,miR-424分别为0.806、≤6.61,IGF-1分别为0.751、≤106.25 ng/mL(P<0.05);sdLDL+miR-424+IGF-1预测脑梗死预后不良的AUC、敏感度、特异度分别为0.896、75.00%、92.92%(P<0.05);脑梗死预后不良患者sdLDL水平与miR-424、IGF-1呈负相关,miR-424与IGF-1呈正相关(P<0.05)。结论血清sdLDL、miR-424、IGF-1表达与脑梗死斑块性质、梗死面积、溶栓治疗效果、预后有关,能相互影响并参与脑梗死发病与病情的进展,检测三者表达有望成为预测患者预后新的生物标志物。

关键词(KeyWords)： 脑梗死;小而密低密度脂蛋白胆固醇;微小RNA-424;胰岛素样生长因子-1;溶栓治疗;受试者工作特征曲线

Abstract:

Keywords:

基金项目(Foundation): 2018年度河南省医学科技攻关计划项目(编号:2018020768);; 河南省2017年科技发展计划项目(编号:172102310205)

作者(Authors): 何诺;谢林森;董丽;任江龙;

参考文献(References)：

• [1] HURFORD R,WOLTERS F J,LI L,et al.Prevalence,predictors,and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke:a population-based cohort study[J].Lancet Neurol,2020,19(5):413-421.DOI:10.1016/S1474-4422(20)30079-X.
• [2] HERMANN D M,BASSETTI C L,MARX U,et al.Refining endpoints for stroke recovery trials[J].Lancet Neurol,2020,19(5):381-382.DOI:10.1016/S1474-4422(20)30101-0.
• [3] 刘春林,徐祥辉,陈惠云,等.支架取栓治疗急性脑梗死临床效果的单中心研究[J].中国实用神经疾病杂志,2020,23(3):206-211.DOI:10.12083/SYSJ.2020.03.043.
• [4] SAKAI K,KOBA S,NAKAMURA Y,et al.Small dense low-density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease[J].Geriatr Gerontol Int,2018,18(6):965-972.DOI:10.1111/ggi.13287.
• [5] WANG M,LIU R.CXCL16 protects against oxygen and glucose deprivation-induced injury in human microvascular endothelial cells-1:Potential role in ischemic stroke[J].J Cell Physiol,2019,234(11):20149-20160.DOI:10.1002/jcp.28616.
• [6] SUN P,ZHANG K,HASSAN S H,et al.Endothelium-Targeted Deletion of microRNA-15a/16-1 Promotes Poststroke Angiogenesis and Improves Long-Term Neurological Recovery[J].Circ Res,2020,126(8):1040-1057.DOI:10.1161/CIRCRESAHA.119.315886.
• [7] ?BERG N D,GADD G,?BERG D,et al.Relationship between Levels of Pre-Stroke Physical Activity and Post-Stroke Serum Insulin-Like Growth Factor I[J].Biomedicines,2020,8(3):E52.DOI:10.3390/biomedicines8030052.
• [8] BOYNE P,MEYROSE C,WESTOVER J,et al.Effects of Exercise Intensity on Acute Circulating Molecular Responses Poststroke[J].Neurorehabil Neural Repair,2020,34(3):222-234.DOI:10.1177/15459683198 99915.
• [9] ERLANDSSON M C,LYNGFELT L,?BERG N D,et al.Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis[J].BMC Med,2019,17(1):141.DOI:10.1186/s12916-019-1374-x.
• [10] 中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51(9):666-682.DOI:10.3760/cma.j.issn.1006-7876.2018.09.004.
• [11] 蔡智立,何奕涛,周致帆,等.脑梗死超早期静脉溶栓治疗的疗效及相关因素分析[J].中国实用神经疾病杂志,2020,23(5):380-385.DOI:10.12083/SYSJ.2020.05.195.
• [12] 闫丙川.阿替普酶静脉溶栓前应用抗血小板药物对急性脑梗死患者疗效的影响[J].中国实用神经疾病杂志,2019,22(8):859-865.
• [13] CHENG X,KAN P,MA Z,et al.Exploring the potential value of miR-148b-3p,miR-151b and miR-27b-3p as biomarkers in acute ischemic stroke[J].Biosci Rep,2018,38(6):BSR20181033.DOI:10.1042/BSR20181033.
• [14] GAREEV I F,BEILERLY O A,NAZAROV V V.MicroRNA and their potential role in the pathogenesis of hemorrhagic stroke[J].Zh Vopr Neirokhir Im N N Burdenko,2020,84(1):86-93.DOI:10.17116/neiro20208401186.
• [15] ZHAO H P,LIU P,XU C M,et al.Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients[J].Chin J Integr Med,2019,25(8):590-597.DOI:10.1007/s11655-018-2843-3.
• [16] XIANG Y,ZHANG Y,XIA Y,et al.LncRNA MEG3 targeting miR-424-5p via MAPK signaling pathway mediates neuronal apoptosis in ischemic stroke[J].Aging (Albany NY),2020,12(4):3156-3174.DOI:10.18632/aging.102790.
• [17] ZHAO H,LI G,WANG R,et al.MiR-424 prevents astrogliosis after cerebral ischemia/reperfusion in elderly mice by enhancing repressive H3K27me3 via NFIA/DNMT1 signaling[J].FEBS J,2019,286(24):4926-4936.DOI:10.1111/febs.15029.
• [18] LI G,MA Q,WANG R,et al.Diagnostic and Immunosuppressive Potential of Elevated Mir-424 Levels in Circulating Immune Cells of Ischemic Stroke Patients[J].Aging Dis,2018,9(2):172-181.DOI:10.14336/AD.2017.0602.
• [19] CAO Y X,WANG Z Q,KANG J X,et al.miR-424 protects PC-12 cells from OGD-induced injury by negatively regulating MKP-1[J].Eur Rev Med Pharmacol Sci,2018,22(5):1426-1436.DOI:10.26355/eurrev_201803_14490.
• [20] ZHANG Y Z,WANG J,XU F.Circulating miR-29b and miR-424 as Prognostic Markers in Patients with Acute Cerebral Infarction[J].Clin Lab,2017,63(10):1667-1674.DOI:10.7754/Clin.Lab.2017.170420.
• [21] GRUNSEICH C,MILLER R,SWAN T,et al.Safety,tolerability,and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy:a randomised,placebo-controlled trial[J].Lancet Neurol,2018,17(12):1043-1052.DOI:10.1016/S1474-4422(18)30320-X.
• [22] SHAHEEN H,SOBHY S,EL MOUSLY S,et al.Insulin-Like Growth Factor-1 in Acute Ischemic Stroke[J].Egypt J Neurol Psychiatr Neurosurg,2018,54(1):42.DOI:10.1186/s41983-018-0042-y.
• [23] PLOUGHMAN M,ESKES G A,KELLY L P,et al.Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke[J].Neurorehabil Neural Repair,2019,33(3):199-212.DOI:10.1177/1545968319832605.
• [24] KING M,KELLY L P,WALLACK E M,et al.Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke[J].Neurol Res,2019,41(4):354-363.DOI:10.1080/01616412.2018.1564451.
• [25] POKHAREL Y,MOUHANNA F,NAMBI V,et al.ApoB,small-dense LDL-C,Lp(a),LpPLA2 activity,and cognitive change[J].Neurology,2019,92(22):e2580-e2593.DOI:10.1212/WNL.0000000000007574.
• [26] QIAO Z X,AI G M,TONG W,et al.Correlation between of small dense low-density lipoprotein cholesterol with acute cerebral infarction and carotid atherosclerotic plaque stability[J].J Clin Lab Anal,2019,33(6):e22891.DOI:10.1002/jcla.22891.
• [27] BENDZALA M,SABAKA P,CAPRNDA M,et al.Atherogenic index of plasma is positively associated with the risk of all-cause death in elderly women:A 10-year follow-up[J].Wien Klin Wochenschr,2017,129(21/22):793-798.DOI:10.1007/s00508-017-1264-1.