诊断学理论与实践 ›› 2024, Vol. 23 ›› Issue (04): 405-415.doi: 10.16150/j.1671-2870.2024.04.009
谷天艳1,3, 潘镜余2, 陈玲3, 邹志浩4, 史清海3()
收稿日期:
2024-01-02
接受日期:
2024-06-03
出版日期:
2024-08-25
发布日期:
2024-08-25
通讯作者:
史清海 E-mail: shiqinghai@aliyun.com
GU Tianyan1,3, PAN Jingyu2, CHEN Lin3, ZOU Zhihao4, SHI Qinghai3()
Received:
2024-01-02
Accepted:
2024-06-03
Published:
2024-08-25
Online:
2024-08-25
摘要:
目的:探讨脑出血患者脑脊液中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素6(Interleukin-6,IL-6)、IL-8水平与病情严重程度的关系和预测患者预后的价值。方法:收集2023年3月至2023年12月间新疆军区总医院神经外科收治的40例新发脑出血患者(发病24 h内入院),另选取同期40例患者作为对照组(对照组患者为存在临床症状而于本院接受脑脊液检查者,但最终排除中枢神经系统疾病)。分别采集入院首次脑脊液和血清标本,收集研究对象的临床资料和实验室检测结果(血清、脑脊液样本中炎性细胞因子TNF-α、IL-6、IL-8水平)。根据入院时格拉斯哥昏迷(Glasgow coma scale,GCS)评分将患者分为轻中度组(GCS 9~15分,14例)和重度组(GCS 3~8分,26例);按照出血量分为≥30 mL组(21例)和<30 mL组(19例)。根据脑出血患者出院后90 d的格拉斯哥预后评分(Glasgow out-come scale,GOS),将脑出血患者分为预后良好组(GOS 4~5分,18例)和预后不良组(GOS 1~3分,22例)。采用Spearman相关系数相关性分析和受试者操作特征(receiver operating characteristic,ROC)曲线分析血清、脑脊液中炎性细胞因子预测脑出血患者预后的价值。结果:与对照组比较,脑出血组血清、脑脊液中TNF-α、IL-6和IL-8水平均显著升高(P<0.001),重度脑出血组血清、脑脊液中TNF-α、IL-6和IL-8水平高于轻中度组(P<0.01),且与GCS评分均呈负相关(r=-0.397、P<0.05;r=-0.587、P<0.01;r=-0.615、P<0.01;r=-0.696、P<0.01;r=-0.671、P<0.01;r=-0.510、P<0.01)。与出血量<30 mL组患者相比,≥30 mL组患者的脑脊液中TNF-α、IL-6、IL-8水平均升高(P<0.05),但在血清中仅IL-6水平升高(P<0.05)。预后不良组血清和脑脊液中的TNF-α、IL-6和IL-8水平较预后良好组升高(P<0.01)。ROC曲线分析显示,脑出血患者入院24 h内脑脊液中TNF-α、IL-6、IL-8单项和联合检测预测脑出血患者预后的曲线下面积(area under the receiver operating characteristic curve, AUC)分别为0.836、0.773、0.849、0.917,患者入院24 h内血清TNF-α、IL-6、IL-8单项和联合检测预测脑出血患者预后的AUC分别为0.692、0.808、0.721、0.843。结论:脑出血患者脑脊液中TNF-α、IL-6和IL-8水平升高,且与患者病情严重程度相关。入院24 h内脑脊液中这些指标的水平可能可以用于预测其出院后90 d的预后。
中图分类号:
谷天艳, 潘镜余, 陈玲, 邹志浩, 史清海. 炎性细胞因子TNF-α、IL-6、IL-8预测新发脑出血患者预后的价值[J]. 诊断学理论与实践, 2024, 23(04): 405-415.
GU Tianyan, PAN Jingyu, CHEN Lin, ZOU Zhihao, SHI Qinghai. The value of inflammatory cytokines(TNF-α, IL-6 and IL-8) in predicting prognosis in patients with new-onset intracerebral hemorrhage[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(04): 405-415.
表1
研究组与对照组基线资料比较
Characteristic | ICH group (n=40) | Control group (n=40) | t/χ2 value | P value |
---|---|---|---|---|
Age (years) | 59.10±12.84 | 58.93±12.52 | 0.051 | 0.960 |
Sex [n (%)] | 0.054 | 0.816 | ||
Male | 26(65) | 25(62.5) | ||
Female | 14(35) | 15(37.5) | ||
Hypertensive [n (%)] | 18(45) | 13(32.5) | 1.317 | 0.251 |
Diabetes [n (%)] | 6(15) | 8(20) | 0.346 | 0.556 |
Cardiology [n (%)] | 3(7.5) | 5(12.5) | 0.556 | 0.456 |
BMI (kg/m2) | 23.49±4.16 | 22.22±3.42 | 1.550 | 0.125 |
表2
预后良好组与预后不良组的各项指标的比较
Characteristic | Favorable(n=18) | Unfavorable(n=22) | t/χ2/Z value | P value |
---|---|---|---|---|
Age (years) | 56.39±14.37 | 61.91±12.04 | 1.323 | 0.194 |
Sex [n (%)] | 0.559 | 0.455 | ||
Male | 12 (66.7) | 17 (77.3) | ||
Female | 6 (33.3) | 5 (22.7) | ||
Hypertensive [n (%)] | 5 (27.8) | 13 (59.1) | 3.922 | <0.05 |
Diabetes [n (%)] | 2 (11.1) | 4 (18.2) | 0.388 | 0.533 |
Cardiology [n (%)] | 2 (7.1) | 1 (12.5) | 0.615 | 0.433 |
Hematoma location [n (%)] | 1.397 | 0.806 | ||
Basal ganglia | 8 (44.4) | 11 (50) | ||
Thalamus | 3 (16.7) | 5 (22.7) | ||
Lobar | 4 (22.2) | 2 (9.1) | ||
Other | 3 (16.7) | 4 (18.2) | ||
GCS (points) | 10.56±3.49 | 5.68±2.06 | -5.502 | <0.000 1 |
ICH volume(mL) [n (%)] | 4.821 | <0.05 | ||
≥30 mL | 6 (33.3) | 15 (68.2) | ||
<30 mL | 12 (66.7) | 7 (31.8) | ||
Blood sugar (mmol/L) | 6.57 (5.58, 7.13) | 10.16 (7.78, 12.90) | -3.833 | <0.000 1 |
Albumin (g/L) | 39.28±3.77 | 36.96±4.03 | -1.866 | 0.070 |
Calcitonin (ng/mL) | 0.27 (0.06, 0.57) | 0.10 (0.26, 0.73) | -0.802 | 0.422 |
WBC (109/L) | 9.92 (7.61, 12.43) | 10.68 (9.01, 12.70) | -0.802 | 0.423 |
D-dimer (mg/L) | 1.47 (0.36, 2.55) | 1.88 (1.08, 6.03) | -1.495 | 0.135 |
表3
脑出血患者功能预后的影响因素分析
Cytokines | β value | SE | Wald value | OR (95%CI) | P value |
---|---|---|---|---|---|
TNF-α in CSF | 0.166 | 0.068 | 6.009 | 1.181 (1.034, 1.349) | 0.014 |
TNF-α in serum | 0.013 | 0.005 | 6.060 | 1.013 (1.003, 1.023) | 0.014 |
IL-6 in CSF | 1.702 | 0.845 | 4.054 | 1.000 (1.000, 1.001) | 0.044 |
IL-6 in serum | 0.093 | 0.034 | 7.230 | 1.097 (1.025, 1.174) | 0.007 |
IL-8 in CSF | 0.001 | 0.000 | 6.888 | 1.001 (1.000, 1.002) | 0.009 |
IL-8 in serum | 0.023 | 0.008 | 7.773 | 1.023 (1.007, 1.040) | 0.005 |
GCS | -0.600 | 0.187 | 10.330 | 0.549 (0.381, 0.791) | 0.001 |
ICH volume | 1.455 | 0.678 | 4.609 | 4.286 (1.135, 16.18) | 0.032 |
表4
血清TNF-α、IL-6、IL-8水平以及联合对脑出血预后预测价值分析
Cytokines | AUC | Sensitivity (%) | Specificity (%) | 95%CI | Youden index | Cutoff value (pg/mL) | P value |
---|---|---|---|---|---|---|---|
TNF-α | 0.692 | 86.4 | 55.6 | 0.524-0.860 | 0.42 | 73.69 | 0.038 8 |
IL-6 | 0.808 | 77.3 | 88.9 | 0.662-0.953 | 0.662 | 12.79 | 0.000 9 |
IL-8 | 0.721 | 90.9 | 50.0 | 0.559-0.883 | 0.409 | 13.09 | 0.017 4 |
Combine | 0.843 | 81.8 | 77.8 | 0.720-0.967 | 0.596 | — | 0.000 2 |
表5
脑脊液TNF-α、IL-6、IL-8水平以及联合对脑出血预后预测价值分析
Cytokines | AUC | Sensitivity (%) | Specificity (%) | 95%CI | Youden index | Cutoff value (pg/mL) | P value |
---|---|---|---|---|---|---|---|
TNF-α | 0.836 | 63.6 | 100 | 0.711-0.961 | 0.636 | 15.60 | 0.000 3 |
IL-6 | 0.773 | 54.5 | 94.4 | 0.628-0.918 | 0.489 | 3 281.96 | 0.003 3 |
IL-8 | 0.849 | 68.2 | 94.4 | 0.732-0.965 | 0.626 | 1 982.95 | 0.000 2 |
Combine | 0.917 | 72.7 | 100 | 0.835-0.999 | 0.727 | — | 0.000 1 |
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