缺血性脑卒中发生及疗效相关的血清分子标志物研究

Ischemic cerebral stroke and its therapeutic effect-related serum markers

目的本研究系统分析了炎性细胞因子与急性缺血性脑卒中发生、发展以及预后的相关性。方法选择2018年8月~2019年3月上海市第八人民医院神经内科收治的急性缺血性脑卒中(AIS)患者54例(AIS组),短暂性脑缺血发作(TIA)患者32例(TIA组)。另选同期与AIS组年龄和性别匹配的健康体检者54例(对照1组),与TIA组年龄和性别匹配的健康体检者32例(对照2组)。使用Bio-Plex Pro平台系统分析血清中15种细胞因子水平的变化,包括白细胞介素(IL)1β,IL-4,IL-6,IL-10,IL-17A,TNF-α,干扰素ɡ,IL-17F,IL-21,IL-22,IL-23,IL-25,IL-31,IL-33,可溶性细胞表面分化抗原40配体(sCD40L)。进而建立疾病发生预测模型,并在TIA患者中检验其可靠性。最后评估AIS患者出院3个月及6个月的2次随访记录。结果AIS组血清IL-1β、IL-4、IL-6、IL-10、干扰素ɡ、TNF-α、IL-17F、IL-21、IL-22、IL-23、IL-31、IL-33、sCD40L水平明显高于对照1组,差异有统计学意义(P<0.05,P<0.01)。TIA组IL-1β、IL-4、IL-10、IL-17A、干扰素ɡ、IL-17F、IL-21、IL-22、IL-23、IL-25及IL-33水平明显高于对照2组,差异有统计学意义(P<0.05,P<0.01)。IL-21作为AIS发生最合理的生物标志物,敏感性为93.8%,特异性为53.1%,曲线下面积为0.777(95%CI:0.659~0.895,P=0.000)。AIS患者IL-1β与脑梗死面积呈正相关(r=0.322,P=0.005),与NIHSS评分呈负相关(r=-0.390,P=0.003)。随访3个月,9例患者复发再次入院,IL-17A水平明显低于未复发患者,差异有统计学意义(P=0.001)。结论缺血性脑卒中患者血清多种细胞因子水平显著变化,在脑卒中的临床诊断、疾病严重程度及预后判断等方面具有潜在的临床应用价值。

Objective To analyze the relationship of inflammatory cytokines with the occurrence,development and outcome of acute ischemic stroke(AIS).Methods Fifty-four AIS patients and 32 transient ischemic attack(TIA)patients admitted to Shanghai No.8 People's Hospital from August 2018 to March 2019 served as AIS group and TIA group respectively with 54 and 32 ageand sex-matched persons undergoing physical examination during the same period served as control group 1 and control group 2 respectively.The changes in serum levels of IL-1β,IL-4,IL-6,IL-10,IL-17A,TNF-α,interferon-ɡ,IL-17F,IL-21,IL-22,IL-23,IL-25,IL-31,IL-33 and sCD40L were analyzed using the Bio-plex Proplatform.A disease prediction model was established and its reliability was tested in TIA patients.The follow-up data of AIS patients were assessed at months 3 and 6 after discharge.Results The serum levels of IL-1β,IL-4,IL-6,IL-10,interferon-ɡ,TNF-α,IL-17F,IL-21,IL-22,IL-23,IL-31,IL-33 and sCD40L were significantly higher in AIS group than in control group 1(P<0.05,P<0.01).The serum levels of IL-1β,IL-4,IL-10,IL-17A,interferon-ɡ,IL-17F,IL-21,IL-22,IL-23,IL-25,and IL-33 were significantly higher in TIA group than in control group 2(P<0.05,P<0.01).As a most rational biomarker for AIS,the sensitivity of IL-21 for the diagnosis of AIS was 93.8% and the specificity of IL-21 for the diagnosis of AIS was 53.1%.The AUC for IL-21 in diagnosis of AIS was 0.777(95%CI:0.659-0.895,P=0.000).IL-1βwas positively related with the infarct size and negatively related with the NIHSS score in AIS patients(r=0.322,P=0.005;r=-0.390,P=0.003).Nine patients were readmitted due to recurrence of AIS during the 3-month follow-up period.The serum IL-17A level was significantly lower in AIS patients with reccurrence of AIS than in those without reccurrence of AIS(P=0.001).Conclusion Significant change in serum levels of cytokines contributes to the clinical diagnosis of ischemic stroke,judgment of its severity and outcome.