Cao S S, Lin A L, Sun L, Liang H, Cheng Y, Xu Y W
Tianjin Medical University General Hospital, Tianjin Neurology Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China.
Zhonghua Yi Xue Za Zhi. 2018 Apr 3;98(13):992-997. doi: 10.3760/cma.j.issn.0376-2491.2018.13.008.
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. (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, =87) and TIA-CI group (=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. (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) cm(3) vs 2.4(0.5, 22.8) cm(3,) (2.5±3.2) mg/L vs (6.2±3.2) mg/L, all <0.05) . hs-CRP was positively correlated with END (=0.311, <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(=1.754, <0.05; =1.858, <0.05; =0.609, <0.05; =0.519, <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. 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.
探讨前循环短暂性脑缺血发作（TIA）对同侧缺血性脑卒中患者早期神经功能恶化（END）的影响及其机制。（1）选取2014年11月至2015年7月在天津医科大学总医院神经内科就诊的113例同侧缺血性脑卒中患者及36例健康志愿者（健康对照组）纳入本研究。根据缺血性脑卒中发生前是否有TIA，将患者分为单纯缺血性脑卒中组（CI组，n = 87）和TIA-CI组（n = 26）。比较两组患者的END、美国国立卫生研究院卒中量表（NIHSS）评分、3个月改良Rankin量表（mRS）评分、梗死灶大小、血清超敏C反应蛋白（hs-CRP）及其他危险因素。（2）于缺血性脑卒中发病后24小时、第3天、第7天和第12天，分别采集TIA-CI组和CI组患者外周血单个核细胞（PBMCs），同时采集对照组PBMCs。采用蛋白质免疫印迹法检测核因子κB（NF-κB）的表达，免疫荧光法检测NF-κB的胞质至核穿梭。（1）TIA-CI组的END发生率、出院时NIHSS评分、3个月mRS评分及血清hs-CRP水平均显著低于CI组，梗死灶大小也显著小于CI组（11.5% 对31.0%，1.9±2.3对3.3±3.7，0.9±0.8对1.8±1.8，1.1（0.3，2.5）cm³对2.4（0.5，22.8）cm³，（2.5±3.2）mg/L对（6.2±3.2）mg/L，均P < 0.05）。hs-CRP与END呈正相关（r = 0.311，P < 0.05）。（2）NF-κB表达：①与对照组相比，两组患者NF-κB表达均先升高后降低，且TIA-CI组较CI组降低更早。②各时间点TIA-CI组NF-κB表达均低于CI组（P = 1.754，P < 0.05；P = 1.858，P < 0.05；P = 0.609，P < 0.05；P = 0.519，P < 0.05）。（3）NF-κB活性：对照组NF-κB大多处于失活状态，位于胞质。缺血性脑卒中后24小时和第3天，TIA-CI组和CI组NF-κB被激活并从胞质转位至核内。第7天和第12天，TIA-CI组NF-κB在核内的聚集减少，大多位于胞质，而CI组NF-κB大多仍位于核内。TIA-CI组NF-κB的激活状态持续时间短于CI组。TIA可降低同侧缺血性脑卒中患者END的发生率。其保护作用可能与抑制NF-κB诱导的炎症反应有关。
