急性缺血性脑卒中患者脑梗死面积与细胞因子和免疫状态的关联性分析

苏醒麒, 赵灵敏, 马迪, 尤久琳, 陈盈, 冯良枢, 王晶, 冯加纯, 王川

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吉林大学学报(医学版) ›› 2025, Vol. 51 ›› Issue (1) : 124-132. DOI: 10.13481/j.1671-587X.20250115
临床研究

急性缺血性脑卒中患者脑梗死面积与细胞因子和免疫状态的关联性分析

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Analysis on correlation of cerebral infarct area with cytokines and immune status in patients with acute ischemic stroke

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摘要

目的 探讨急性缺血性脑卒中患者的脑梗死面积与细胞因子和免疫状态的关联性,为不同程度脑梗死患者的免疫治疗提供理论依据。 方法 根据纳入标准和排除标准选取发病72 h内的67例急性缺血性脑卒中患者作为研究对象,根据磁共振弥散加权成像(DWI)序列的最大梗死层面面积将患者分为大面积脑梗死组(n=34)和非大面积脑梗死组(n=33)。收集2组患者的性别、年龄和既往病史等临床基线资料,采用流式细胞术检测2组患者血清中白细胞介素(IL)-2、IL-6、IL-10、IL-17A、肿瘤坏死因子α(TNF-α)和干扰素γ(IFN-γ)水平,计算2组患者外周血中淋巴细胞绝对值(LYM#)、淋巴细胞百分比(LYM%)和中性粒细胞/淋巴细胞比值(NLR),同时计算IFN-γ/IL-4比值、TNF-α/IL-4比值和TNF-α/IL-10比值;并依据临床神经专科查体体征评价2组患者美国国立卫生研究院卒中量表(NIHSS)评分;采用秩相关分析检验2组患者脑梗死面积与NIHSS评分、细胞因子和免疫状态之间的相关性。 结果 与非大面积脑梗死组比较,大面积脑梗死组患者血清中IL-2、IL-6、IL-10、IL-17A、TNF-α和IFN-γ水平以及外周血中NLR均明显升高(P<0.01),LYM#、LYM%和TNF-α/IL-4比值明显降低(P<0.01)。秩相关分析,大面积脑梗死组患者脑梗死面积与患者NIHSS评分呈正相关关系(rs =0.521,P<0.05),非大面积脑梗死组患者脑梗死面积与患者NIHSS评分呈明显正相关关系(rs =0.721,P<0.001)。2组患者的NIHSS评分与血清中IL-6(rs =0.306,P=0.005)、IL-4(rs =0.252,P<0.001)、IL-2(rs =0.109,P=0.025)、IL-17A(rs =0.405,P<0.001)和IFN-γ(rs =0.146,P<0.001)水平均呈正相关关系;NIHSS评分与TNF-α(rs =0.039,P=0.726)和IL-10(rs =0.121,P=0.192)水平无相关性。2组患者的NIHSS评分与血清中LYM#(rs =-0.026,P=0.036)和LYM%(rs =-0.008,P=0.002)呈负相关关系,与NLR呈正相关关系(rs =0.315,P=0.009)。 结论 急性脑梗死患者的梗死面积与NIHSS评分、炎症反应、适应性免疫损伤程度和免疫状态具有相关性,细胞因子和免疫指标也与梗死面积总体呈正相关关系;与非大面积脑梗死患者比较,大面积脑梗死患者更易发生免疫抑制。

Abstract

Objective To explore the correlations between the cerebral infarction area and cytokines and immune status in patients with acute ischemic stroke, and to provide the theoretical basis for immunotherapy of the patients with different degrees of cerebral infarction. Methods Sixty-seven patients with acute ischemic stroke within 72 h of the onset were randomly selected according to the inclusion and exclusion criteria, and were divided into large-area cerebral infarction group (n=34) and non-large-area cerebral infarction group(n=33) on the basis of the biggest infarction area in the sequences of magnetic resonance diffusion-weighted imaging(CDWI). Clinical baseline characteristics such as gender, age, and medical history were collected from the patients in two groups, the serum levels of interleukin (IL)-2, IL-6, IL-10, and IL-17A, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured using flow cytometry; the absolute values of lymphocytes (LYM#), lymphocyte percentages (LYM%), and neutrophil/lymphocy ratios(NLR) in peripheral blood of the patients caiculated, and the ratios of IFN-γ/IL-4, TNF-α/IL-4, and TNF-α/IL-10 rations were also calculated. The values of National Institutes of Health Stroke Scale (NIHSS) scores of the patients were evaluatd on the basis of the assessment of clinical neurological signs. The correlations of the cerebral infarction area and NIHSS score, cytokines and immune status groups of the patients in two were tested by rank correlation analysis. Results Compared with non-large-area cerebral infarction group, the serum levels of IL-2, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ as well as the NLR in the peripheral blood of the patients in large-area cerebral infarction group were significantly increased (P<0.01), while the LYM#, LYM% and TNF-α/IL-4 were significantly decreased (P<0.01). There was a positive correlation between cerebral infarction area and NIHSS score in the patients in large-area cerebral infarction group (rs =0.521, P<0.05), and there was a significantly positive correlation between cerebral infarct area and NIHSS score in the patients in non-large-area cerebral infarction group (rs =0.721, P<0.001). The NIHSS scores were positively correlated with serum IL-6 (rs =0.306, P=0.005), IL-4 (rs =0.252, P<0.001), IL-2 (rs =0.109, P=0.025), IL-17A (rs =0.405, P<0.001), and IFN-γ (rs =0.146, P<0.001) levels in two groups; no correlations were found between NIHSS scores and TNF-α (rs =0.039, P=0.726) and IL-10 (rs =0.121, P=0.192) levels. NIHSS scores of the patients in two groups had negative correlatious with the serum level of LYM# (rs =-0.026, P=0.036) and LYM% (rs =-0.008, P=0.002) ,and had positive correlated with NLR (rs =0.315, P=0.009). Conclusion The infarction area of the patients with actue cerebral infarction is correlated with the NIHSS score, the inflammatory response, the degree of adaptive immune injury, and the immune status. The have positive correlation with cytokines and immune markers and the overall size of the infarction area. Compared with the patients with non-large-acea cerebral infarction, the immunosuppression of the patients with large-area infarcted areas is more likely to occure.

关键词

急性脑梗死 / 免疫 / 炎症 / 细胞因子 / 炎性细胞 / 梗死面积 / 美国国立卫生研究院卒中量表评分

Key words

Acute cerebral infarction / Immunity / inflammation / Cytokines / Inflammatory cells / Infarct size / National Institutes of Health Stroke Scale score

中图分类号

R781.42

引用本文

导出引用
苏醒麒 , 赵灵敏 , 马迪 , . 急性缺血性脑卒中患者脑梗死面积与细胞因子和免疫状态的关联性分析. 吉林大学学报(医学版). 2025, 51(1): 124-132 https://doi.org/10.13481/j.1671-587X.20250115
Xingqi SU, Lingmin ZHAO, Di MA, et al. Analysis on correlation of cerebral infarct area with cytokines and immune status in patients with acute ischemic stroke[J]. Journal of Jilin University(Medicine Edition). 2025, 51(1): 124-132 https://doi.org/10.13481/j.1671-587X.20250115

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作者贡献声明

苏醒麒和赵灵敏参与数据收集、整理及统计学分析以及论文撰写,尤久琳、陈盈、冯良枢和王晶参与研究选题及统计学分析,马迪、冯加纯和王川参与研究选题、论文修改及审校。

基金

国家自然科学基金项目(82071289)
吉林省科技厅自然科学基金项目(YDZJ202201ZYTS037)

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