短暂性脑缺血发作对后续脑梗死早期神经功能恶化的影响及机制被引量：28

Effect of transient ischemic attack on early neurological deterioration in patients with ipsilateral ischemic stroke

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摘要目的探讨前循环同侧短暂性脑缺血发作（TIA）对后续脑梗死早期神经功能恶化（END）的影响及可能机制。方法（1）收集2014年11月至2015年7月于天津医科大学总医院神经内科住院的前循环梗死患者113例，另选取健康对照组36名。将梗死患者分为单纯脑梗死组（CI组）87例和TIA后脑梗死组（TIA-CI组）26例，比较2组早期神经功能恶化（END）比例、美国国立卫生研究院卒中量表（NHISS）评分、出院3个月时改良Rankin量表（mRS）评分、脑梗死体积、高敏C反应蛋白（hs-CRP）水平及其他相关危险因素。（2）分别留取TIA-CI组、CI组患者梗死后24 h、3 d、7 d、12 d及健康对照组的外周静脉血，提取单个核细胞，采用Western印迹法、免疫荧光染色法分别检测核因子-κB（NF-κB）的表达、活性。结果（1）TIA-CI组发生END比例（11.5%比31.0%），出院NIHSS评分[（1.9±2.3）分比（3.3±3.7）分]、3个月mRS评分[（0.9±0.8）分比（1.8±1.8）分]低于CI组，脑梗死体积[1.1（0.3, 2.5） cm3比2.4（0.5, 22.8） cm3]小于CI组，hs-CRP[（2.5±3.2） mg/L比（6.2±3.2） mg/L]水平低于CI组，均P〈0.05；hs-CRP与END呈正相关（r＝0.311, P〈0.05）。（2）NF-κB表达检测：①与健康对照组相比，两梗死组NF-κB表达均呈先上升后下降趋势，TIA-CI组下降早于CI组。②TIA-CI组梗死24 h、3 d、7 d、12 d时NF-κB表达均低于CI组（t＝1.754, P〈0.05; t＝1.858, P〈0.05; t＝0.609, P〈0.05; t＝0.519, P〈0.05）。（3）NF-κB活性检测：健康对照组NF-κB大部分位于胞质内，处于失活状态。与健康对照组相比，梗死24 h、3 d时TIA-CI组、CI组NF-κB均发生核移位，活性增加；7 d、12 d时，TIA-CI组NF-κB在胞核中聚集减少，大部分位于胞质内，而CI组NF-κB仍大部分位于胞核内。与CI组相比，TIA-CI组NF-κB的活化状态持续时间较短。结论 TIA可减少后续梗死END的发生，其作用机制可能与抑制NF-κB介导的炎症反应有关。 Objective To explore the effect of anterior circulation transient ischemic attack （TIA） on early neurological deterioration （END） in patients with ipsilateral ischemic stroke and its mechanism.Methods （1） One hundred and thirteen patients with ipsilateral ischemic stroke and 36 healthy volunteers （healthy control group） in Neurology Department of Tianjin Medical University General Hospital from November 2014 to July 2015 were recruited into this study. According to whether got TIA before ischemic stroke, patients were divided into simple ischemic stroke group （CI group, n=87） and TIA-CI group （n=26）. Their END, NIHSS score, 3-month mRS score, infarct size, serum hs-CRP and other risk factors were compared. （2） The peripheral blood mononuclear cells （PBMCs） were extracted from peripheral blood of TIA-CI group and CI group at 24 h, the 3 th day, the 7 th day and 12th day after ischemic stroke onset. At the same time, PBMCs of control group were collected. Western blot was carried out to evaluate the expression of nuclear factor-κB （NF-κB）. Immunofluorescence was used to detect the cytoplasmic-to-nuclear shuttling of NF-κB.Results （1） The incidence of END, NIHSS score at discharge, 3-month mRS score and serum hs-CRP level were significantly lower whereas the infarct size was significantly smaller of TIA-CI group than CI group （11.5% vs 31.0%, 1.9±2.3 vs 3.3±3.7, 0.9±0.8 vs 1.8±1.8, 1.1（0.3, 2.5） cm3 vs 2.4（0.5, 22.8） cm3, （2.5±3.2） mg/L vs （6.2±3.2） mg/L, all P〈0.05） . hs-CRP was positively correlated with END （r=0.311, P〈0.05）. （2） Expression of NF-κB： ① Compared with control group, the NF-κB expression increased first and then decreased in both of the two patient groups, and it decreased earlier in TIA-CI group than CI group.②In each time point, NF-κB expression of TIA-CI group was lower than CI group（t=1.754, P〈0.05; t=1.858, P〈0.05; t=0.609, P〈0.05; t=0.519, P〈0.05）. （3） Activity of NF-κB： Most of NF-κB were inactivation and located in cytoplasm of control group. NF-κB of TIA-CI group and CI group was activated and translocated from cytoplasm into nuclear at the 24 h and 3 th day after ischemic stroke. At the 7 th day and 12th day, the accumulation of NF-κB in nuclear decreased and most of them located in cytoplasm in TIA-CI group, whereas most of NF-κB still located in nuclear in CI group. The activated station of NF-κB lasted shorter in TIA-CI group than CI group.Conclusions TIA can reduce the incidence of END in patients of ipsilateral ischemic stroke. Its protective effect may relate with the inhibition of inflammation which induced by NF-κB.

作者曹杉杉林傲蕾孙莉梁浩程焱徐艳炜 Cao Shanshan, Lin Aolei, Sun Li, Liang Hao, Cheng Yan, Xu Yanwei(Tianjin Medical University General Hospital, Tianjin Neurology Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nebulous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, Chin)

机构地区天津医科大学总医院

出处《中华医学杂志》 CAS CSCD 北大核心 2018年第13期992-997,共6页 National Medical Journal of China

基金国家自然科学基金(81401023,81571201)

关键词脑缺血发作短暂性早期神经功能恶化脑梗死 NF-ΚB Ischemic attack, transient Early neurological deterioration Brain infarction NF-kappaB

分类号 R743.3 [医药卫生—神经病学与精神病学]

作者简介通信作者：徐艳炜 Email：alice811221@hotmail.com

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参考文献3

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