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据最新流行病学调查报告,我国每年新发脑卒中病人约200万人,其中急性脑梗死是最常见类型,约占全部脑卒中的69.6%~70.8%[1]。急性脑梗死病人年致死/致残率高达33.4%~33.8%[2],给社会、家庭及个人带来沉重的负担。因此探讨急性脑梗死的病理生理学机制及其预防、治疗具有重要意义。急性脑梗死后脑组织损伤除与血管闭塞导致脑细胞缺血坏死有关外,还与脑梗死继发的脑内炎性反应关系密切,抑制炎性反应能够减轻脑组织损伤,减小脑梗死体积,促进神经功能恢复[3]。但脑梗死后炎性反应发生、发展的具体机制尚不十分明确。S100钙结合蛋白A12(S100 calcium binding protein A12,S100A12)属于钙结合蛋白家族,与晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)结合后促进多种炎性及免疫反应[4]。RAGE可通过激活其下游信号分子核因子-κB(nuclear factor-κB, NF-κB)促进炎性因子表达和炎性级联反应发生[5]。本研究观测急性脑梗死后血清S100A12、RAGE以及NF-κB水平的动态变化,探讨S100A12/RAGE/NF-κB信号通路与脑梗死严重程度的相关性,从而为干预脑梗死后炎性反应通路相关靶点、改善脑梗死预后提供理论依据。
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纳入我院神经内科2019年1-12月收住的急性脑梗死病人(发病24 h内)82例为观察组,其中男59例,女23例,年龄(63.45 ±9.70)岁。诊断均符合《中国急性期缺血性脑卒中诊治指南2018》标准[6],临床资料完整,并经头颅MRI证实为急性脑梗死。另纳入85例因非脑血管病住院病人为对照组,其中男54例,女31例,年龄(63.48 ±10.75)岁。排除标准:(1)6个月内患有急性脑血管意外;(2)合并其他颅内病变(脑出血、梗死后出血转化、癫痫、颅内感染、肿瘤、血管畸形、静脉窦血栓形成、动脉夹层等);(3)患有严重肝、肾、心脏疾病以及血液系统疾病、肿瘤、感染、自身免疫病等。2组病人之间年龄、性别、合并脑梗死危险因素[高血压、糖尿病、高脂血症、高同型半胱氨酸(HCY)、心房颤动、吸烟等]比较差异均无统计学意义(见表 1)。
分组 n 男 女 年龄/岁 高血压 糖尿病 高脂血症 高HCY 心房颤动 吸烟 观察组 82 59 23 63.44 ± 9.77 73(89.02) 30(36.59) 30(36.59) 21(25.61) 8(9.80) 23(28.05) 对照组 85 54 31 63.48 ± 10.75 60(70.59) 21(24.71) 25(29.41) 14(16.47) 5(5.9) 20(23.53) χ2 — 1.35 0.93* 0.99 1.48 0.49 1.38 0.75 0.26 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示t值 表 1 2组一般资料比较[n; 百分率(%)]
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观察组于入院后1、3、7 d抽取晨间空腹血,以ELISA试剂盒检测血清S100A12、RAGE、NF-κB水平(按说明书步骤操作),并记录1、3、7 d NIHSS评分。对照组于入院后1 d抽取晨间空腹血,以ELISA试剂盒检测血清S100A12、RAGE、NF-κB水平。
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采用t检验、χ2检验、方差分析和二元定距相关分析法。
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观察组各时间点S100A12、RAGE、NF-κB水平与对照组比较差异均有统计学意义(P < 0.05~P < 0.01)。脑梗死后S100A12、RAGE、NF-κB水平1 d时均最高(P < 0.05),3 d和7 d水平差异均无统计学意义(P>0.05)(见表 2)。
分组 时间 S100A12/ (μg/mL) RAGE/ (μg/mL) NF-κB/ (pg/mL) 对照组 21.29±2.79 482.08±107.25 15 60.91±267.42 观察组 1 d 26.05±3.74** 541.27±93.94** 1 779.34±347.88** 3 d 25.66±3.65*△ 526.12±90.36*△ 1 710.76±323.28*△ 7 d 24.97±3.20*△ 518.60±83.91*△ 1 676.80±306.71*△ F 35.42 5.95 7.15 P < 0.01 < 0.01 < 0.01 MS组内 11.301 8 907.300 97 537.768 与对照组比较*P < 0.05,**P < 0.01;与1 d比较△P < 0.05 表 2 2组血清S100A12、RAGE、NF-κB水平比较(x±s)
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脑梗死后1、3、7 d的NIHSS评分分别为(4.00±3.11)、(3.74±3.05)、(3.52±3.06)分。三个时间点S100A12、RAGE、NF-κB水平与相应NIHSS评分均呈正相关关系(P < 0.05~P < 0.01)(见表 3)。
指标 1 d 3 d 7 d S100A12 0.26* 0.25* 0.26* RAGE 0.23* 0.23* 0.24* NF-κB 0.39** 0.28* 0.27* *P < 0.05,**P < 0.01 表 3 不同时间的S100A12、RAGE、NF-κB水平与NIHSS评分相关性(r)
S100A12/RAGE/NF-κB炎性信号通路与急性脑梗死严重程度的相关性
Correlation between S100A12/RAGE/NF-kB inflammatory signal pathway and severity of acute cerebral infarction
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摘要:
目的观察急性脑梗死病人血清中S100钙结合蛋白A12(S100A12)、晚期糖基化终产物受体(RAGE)及核转录因子-κB(NF-κB)的动态变化,并分析其与脑梗死严重程度的相关性。 方法纳入82例急性脑梗死病人为观察组,于入院后1、3、7 d进行美国国立卫生研究院卒中量表(NIHSS)评分,ELISA检测相应时间点血清S100 A12、RAGE及NF-κB水平变化,并与NIHSS评分进行相关性分析;另纳入85例因非脑血管病住院病人为对照组,于入院后1 d检测S100 A12、RAGE及NF-κB水平。 结果观察组1、3、7 d血清S100 A12、RAGE及NF-κB水平均明显高于对照组(P < 0.01);1 d血清S100 A12、RAGE以及NF-κB水平均最高(P < 0.05~P < 0.01);3 d与7 d水平差异均无统计学意义(P>0.05)。相关性分析显示,各时间点血清S100 A12、RAGE及NF-κB水平与相应NIHSS评分均呈正相关关系(P < 0.05~P < 0.01)。 结论脑梗死急性期S100 A12、RAGE及NF-κB水平升高,且与急性脑梗死后神经功能缺损严重程度相关。 -
关键词:
- 脑梗死 /
- S100钙结合蛋白A12 /
- 晚期糖基化终产物受体 /
- 核转录因子-κB
Abstract:ObjectiveTo observe the dynamic changes of S100 calcium binding protein A12(S100A12), receptor for advanced glycation end products(RAGE) and nuclear factor κB(NF-κB) in patients with acute cerebral infarction, and analyze the correlation between them and severity of cerebral infarction. MethodsEighty-two patients with acute cerebral infarction were set as the observation group.On the 1 d, 3 d and 7 d after admission, the NIHSS scores in the observation group were evaluated, the serum levels of S100A12, RAGE and NF-κB were detected using ELISA, and the correlation between the above indexes and NIHSS score was analyzed.Eighty-five patients without cerebrovascular disease were set as the control group, and the serum levels of S100A12, RAGE, NF-κB were detected on the first day after admission. ResultsThe serum levels of S100A12, RAGE and NF-κB in observation group on the 1 d, 3 d and 7 d were significantly higher than those in control group(P < 0.01).The levels of S100A12, RAGE and NF-κB was highest on the 1 d(P < 0.05 to P < 0.01), and tbe differences of which between 3 d and 7 d were not statistically significant(P>0.05).The results of correlation analysis indicated that the serum levels of S100A12, RAGE and NF-κB were positively correlated with NIHSS score at each time point(P < 0.05 to P < 0.01). ConclusionsThe levels of S100A12, RAGE and NF-κB increase, which are related to the severity degree of neurological deficit in patients with acute cerebral infarction. -
表 1 2组一般资料比较[n; 百分率(%)]
分组 n 男 女 年龄/岁 高血压 糖尿病 高脂血症 高HCY 心房颤动 吸烟 观察组 82 59 23 63.44 ± 9.77 73(89.02) 30(36.59) 30(36.59) 21(25.61) 8(9.80) 23(28.05) 对照组 85 54 31 63.48 ± 10.75 60(70.59) 21(24.71) 25(29.41) 14(16.47) 5(5.9) 20(23.53) χ2 — 1.35 0.93* 0.99 1.48 0.49 1.38 0.75 0.26 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示t值 表 2 2组血清S100A12、RAGE、NF-κB水平比较(x±s)
分组 时间 S100A12/ (μg/mL) RAGE/ (μg/mL) NF-κB/ (pg/mL) 对照组 21.29±2.79 482.08±107.25 15 60.91±267.42 观察组 1 d 26.05±3.74** 541.27±93.94** 1 779.34±347.88** 3 d 25.66±3.65*△ 526.12±90.36*△ 1 710.76±323.28*△ 7 d 24.97±3.20*△ 518.60±83.91*△ 1 676.80±306.71*△ F 35.42 5.95 7.15 P < 0.01 < 0.01 < 0.01 MS组内 11.301 8 907.300 97 537.768 与对照组比较*P < 0.05,**P < 0.01;与1 d比较△P < 0.05 表 3 不同时间的S100A12、RAGE、NF-κB水平与NIHSS评分相关性(r)
指标 1 d 3 d 7 d S100A12 0.26* 0.25* 0.26* RAGE 0.23* 0.23* 0.24* NF-κB 0.39** 0.28* 0.27* *P < 0.05,**P < 0.01 -
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