老年急性腔隙性脑梗死患者血清miR-29b和靶蛋白AQP4水平与病情进展和脑白质病变的关系分析

doi:10.19854/j.cnki.1008-2425.2022.01.0010

摘要/Abstract

摘要： 目的为了探讨老年急性腔隙性脑梗死(ALI)患者血清miR-29b和水通道蛋白4(AQP4)水平与病情进展和脑白质病变的相关性。方法选取2018年1月~2018年12月期间在我院神经内科住院的128例老年ALI患者作为研究组,另外选择年龄和性别匹配的60例非脑梗死人群组成对照组;采用实时荧光定量PCR法测定2组血清miR-29b表达水平;采用酶联免疫吸附法测定2组血清中AQP4水平。根据入院和7d NIHSS评分判断早期神经功能障碍(END);根据入院7 d内脑部MRI扫描结果,判断脑白质病变(WMH)面积;随访1年复查脑部MRI,判断脑微出血进展。结果与对照组相比,研究组ALI患者血清miR-29b表达降低,同时血清AQP4水平升高(P＜0.05),且ALI患者血清miR-29b与血清AQP4水平呈负相关性(r=-0.791,P＜0.001)。绘制ROC曲线,血清miR-29b诊断ALI的曲线下面积为0.881(95%CI:0.798~0.934),其诊断效能高于血清AQP4(P＜0.05)。此外,与非END亚组(n=96)相比,END亚组(n=32)ALI患者血清miR-29b表达降低,同时血清AQP4水平升高(P＜0.05)。与WMH轻度病变亚组(n=50)相比,重度病变亚组(n=78)患者血清miR-29b表达降低,同时血清AQP4水平升高(P＜0.05)。与无脑微出血进展亚组(n=104)相比,进展亚组(n=24)患者血清miR-29b表达降低,同时血清AQP4水平升高(P＜0.05)。结论老年ALI患者血清miR-29b表达降低,同时AQP4蛋白水平增加,这与END的发生、WMH病变程度以及随访1年脑微出血进展有关,检测血清miR-29b有望成为ALI早期诊断的生物标志分子。

关键词: 急性腔隙性脑梗死, 老年患者, miR-29b/AQP4, 疾病进展, 脑白质病变

Abstract: Objective To investigate the relationship between serum miR-29b,Aquaporin-4 (AQP4) and disease progression,white matter hyperintensities (WMH) in elderly patients with acute lacunar infarction (ALI).Methods 128 elderly patients with ALI who were hospitalized in the department of Neurology of our hospital from January 2018 to December 2018 were selected as the research group,and 60 subjects with matched age and gender and without any cerebral infarction were selected as the control group.The expression of serum miR-29b was measured by real-time fluorescence quantitative PCR,and the level of serum AQP4 was measured by enzyme-linked immunosorbent assay.Early neurological dysfunction (END) was evaluated according to NIHSS scores on admission and after 7 days; the WMH volume was determined according to the Results of brain MRI scan within 7 days after admission; and the progress of cerebral microbleeds was judged by brain MRI after 1-year follow-up.Results Compared with the control group,the expression of miR-29b in the study group was lower,while the serum AQP4 level was increased (P<0.05),and there was a negative correlation between the serum miR-29b and AQP4 level in ALI patients (r=-0.791,P<0.001).The area under ROC curve of serum miR-29b for the diagnosis of ALI was 0.881 (95%CI:0.798~0.934),which was more than the AUC of serum AQP4 (P<0.05).In addition,compared with the non-END subgroup (n=96),the serum miR-29b expression was decreased and the serum AQP4 level was increased in the END subgroup (n=32) (P<0.05).Compared with WMH mild lesion subgroup(n=50),the serum miR-29b expression was decreased and serum AQP4 level was increased in severe lesion subgroup (n=78) (P<0.05).Compared with the no cerebral microbleeds progressive subgroup (n=104),the serum miR-29b expression was decreased and the serum AQP4 level was increased in the progressive subgroup (n=24) (P<0.05).Conclusion The serum miR-29b expression is decreased,while serum AQP4 protein level is increased in elderly ALI patients,which would be related to the occurrence of END,the degree of WMH lesions and the progress of cerebral microbleeds in one year follow-up.Serum miR-29b would be a potential biomarker for early diagnosis of ALI.

Key words: Acute lacunar infarction, Elderly patients, MiR-29b/AQP4, Disease progression, White matter hyperintensities

中图分类号:

R743

吴海威, 牛玉莲, 陈娜. 老年急性腔隙性脑梗死患者血清miR-29b和靶蛋白AQP4水平与病情进展和脑白质病变的关系分析[J]. 立体定向和功能性神经外科杂志, 2022, 35(1): 48-53.

Wu Haiwei, Niu Yulian, Chen Na. Relationship between serum miR-29b,AQP4 and disease progression,white matter hyperintensities in elderly patients with acute lacunar infarction[J]. Chinese Journal of Stereotactic and Functional Neurosurgery, 2022, 35(1): 48-53.

参考文献

[1] 杨棠,吴波.急性腔隙性脑梗死的诊断进展[J].临床内科杂志,2020,37(6):394~396.
[2] Zhou YN,Gao HY,Zhao FF,et al.The study on analysis of risk factors for severity of white matter lesions and its correlation with cerebral microbleeds in the elderly with lacunar infarction[J].Medicine(Baltimore),2020,99(4):e18865.
[3] 陈蓓蕾,张奥楠,吕友梅,等.老年腔隙性脑梗死患者溶栓治疗后出血性转化的发生情况及其影响因素研究[J].实用心脑肺血管病杂志,2020,28(6):62~67.
[4] 安宏娜,陈玮,吾红光,等.急性脑梗死患者血清AQP1、AQP4、VEGF表达与脑水肿严重程度的关系[J].中国动脉硬化杂志,2019,44(11):956~959,964.
[5] Falcione S,Kamtchum-Tatuene J,Sykes G,et al.RNA expression studies in stroke:what can they tell us about stroke mechanism?[J].Curr Opin Neurol,2020,33(1):24~29.
[6] Altintas O,Ozgen Altintas M,et al.Neuroprotective effect of ischemic preconditioning via modulating the expression of cerebral miRNAs against transient cerebral ischemia in diabetic rats[J].Neurol Res,2016,38(11):1003~1011.
[7] Hou K,Li G,Zhao J,et al.Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway[J].J Neuroinflammation,2020,17(1):46.
[8] 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.中国脑血管疾病分类2015[J].中华神经杂志,2017,50(3):168~171.
[9] Cedres N,Ferreira D,Machado A,et al.Predicting Fazekas scores from automatic segmentations of white matter signal abnormalities[J].Aging(Albany NY),2020,12(1):894~901.
[10] 中国医师协会神经外科学分会神经重症专家委员会.脑卒中病情监测中国多学科专家共识[J].中华医学杂志,2021,101(5):317~326.
[11] Das AS,Regenhardt RW,Feske SK,Gurol ME,et al.Treatment Approaches to Lacunar Stroke[J].J Stroke Cerebrovasc Dis,2019,28(8):2055~2078.
[12] 刘娜,王晓,王培芝,等.老年缺血性脑小血管病危险因素及早期预测模型建立[J].中国老年学杂志,2021,41(8):1582~1585.
[13] Shi YL,Thrippleton MJ,Blair GW,et al.Small vessel disease is associated with altered cerebrovascular pulsatility but not resting cerebral blood flow[J].J Cerebr Blood F Met,2020,40(1):85~99.
[14] 周其达,秦琳,潘晓帆,等.血浆水通道蛋白4水平早期预测恶性大脑中动脉梗死的价值[J].现代医学,2019,44(10):1241~1245.
[15] Shi ZF,Fang Q,Chen Y,et al.Methylene blue ameliorates brain edema in rats with experimental ischemic stroke via inhibiting aquaporin 4 expression[J].Acta Pharmacol Sin,2021,42(3):382~392.
[16] Lee JH,Cui HS,Shin SK,et al.Effect of propofol post-treatment on blood-brain barrier integrity and cerebral edema after transient cerebral ischemia in rats[J].Neurochem Res,2013,38(11):2276~2286.
[17] Liu Y,Ma Y,Du B,et al.Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice[J].Mol Neurobiol,2020,57(9):3891~3901.
[18] Wang Y,Huang J,Ma Y,et al.MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4[J].J Cereb Blood Flow Metab,2015,35(12):1977~1984.
[19] Yadav BK,Oh SY,Kim NK,et al.Association of rs2075575 and rs9951307 polymorphisms of AQP-4 gene with leukoaraiosis[J].J Stroke Cerebrovasc Dis,2014,23(5):1199~1206.
[20] Sato T,Sakai K,Komatsu T,et al.Risk factors for infarct expansion are different between lacunar and giant lacunar infarction[J].Atherosclerosis,2020,292:17~22.
[21] 王光胜,胡婷,杨金建,等.不同临床分型脉络膜前动脉梗死患者影像学特征及其神经功能障碍严重程度影响因素分析[J].实用心脑肺血管病杂志,2020,28(10):113~117.