老年脓毒症患者血清循环Netrin-1表达水平对发生脑损伤风险的预测价值研究

Study on the Value of Serum Circulating Netrin-1 Expression Level in Predicting the Risk of Brain Injury in Elderly Patients with Sepsis

目的 探讨神经导向因子 -1(Netrin-1) 在老年脓毒症并发脑损伤(sepsis-associated encephalopathy,SAE)患者血清中表达情况及临床意义。方法 选择 2017 年 1 月~ 2020 年 12 月在唐山市丰润区人民医院就诊的老年脓毒症患者 162例为观察对象,其中并发脑损伤患者 67 例作为 SAE 组,未并发脑损伤患者 95 例作为对照组;根据患者 28 天内死亡情况,将 SAE 患者分为存活组 35 例和死亡组 32 例。酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清中 Netrin-1 和神经元特异性烯醇化酶(neuron specific enolase,NSE)表达水平,免疫层析法检测中枢神经特异蛋白(S100β)表达水平,对患者进行急性生理健康与慢性疾病(acute physical health and chronic diseases,APACHE Ⅱ)评分、序贯器官衰竭估计(Sequential Organ Failure Assessment, SOFA)评分,Pearson 分析血清 Netrin-1 水平与 NSE,S100β,APACHE Ⅱ和 SOFA 评分相关性,受试者工作特征(receiver operating characteristic,ROC)曲线分析血清 Netrin-1 对 SAE 的预测价值。结果 SAE 患者住重症加强护理病房(intensive care unit, ICU)时间 8.72±1.81 天 , APACHE Ⅱ为 20.10±6.46分和 SOFA 为 11.57±4.83 分,显著高于对照组的 ICU 时间 4.52±1.34 天,APACHE Ⅱ 14.20±5.31 分和 SOFA 8.41±3.56 分,差异均有统计学意义(t=4.794~16.971,均 P < 0.001)。SAE 患者血清 Netrin-1 水平为 114.57±30.21 ng/ml,显著低于对照组(162.81±35.43 ng/ml)的表达水平;NSE 和 S100β 分别为 9.62±1.76 ng/ml 和 1.03±0.32μg/ml,显著高于对照组(7.32±1.35ng/ml 与 0.75±0.21μg/ml),差异均有统计学意义(t=6.723~9.408,均 P < 0.001)。死亡组SAE 患者血清 Netrin-1 水平为 93.78±25.62ng/ml,显著低于存活组的 134.26±28.05ng/ml;NSE 和 S100β 高于存活组(13.01±1.81 ng/ml vs 7.23±1.14 ng/ml;1.29±0.35μg/ml vs 0.81±0.19μg/ml),其 APACHE Ⅱ和 SOFA 显著高于对照组(22.15±6.21 分 vs 18.23±5.64 分;13.25±3.42 分 vs 10.45±2.95 分),差异具有统计学意义(t=2.708~15.782,均 P < 0.05)。相关性分析结果显示,SAE 患者血清 Netrin-1 水平与 NSE,S100β,APACHE Ⅱ和 SOFA 评分呈负相关性(r=-0.451,-0.503,-0.514,-0.409,均 P < 0.001)。血清 Netrin-1 联合 NSE 和 S100β 预测老年脓毒症患者发生脑损伤风险敏感度和特异度分别为 95.52% 和 89.47%(AUC=0.969,95%CI:0.942~0.996,P < 0.001),联合诊断优于血清 Netrin-1 单独检测(AUC=0.873,95%CI:0.819~0.928,P < 0.001)。结论 老年 SAE 患者血清 Netrin-1 水平降低。血清 Netrin-1 单独或联合 NSE 和 S100β 检测对预测老年脓毒症患者发生脑损伤风险具有一定临床应用价值。

Objective To explore the expression and clinical significance of neural guidance factor-1(Netrin-1) in the serum of elderly sepsis patients with brain injury(SAE). Methods A total of 162 elderly patients with sepsis in Tangshan Fengrun People’s Hospital from January 2017 to December 2020 were selected as the observation objects, including 67 patients with brain injury as SAE group and 95 patients without brain injury as control group. Aaccording to the death within 28 days, the patients were divided into survival group(n=35) and death group(n=32). The expression levels of Netrin-1 and neuron specific enolase(NSE) in serum were detected by enzyme-linked immunosorbent assay(ELISA), the expression level of central nerve specific protein(S100 β) was detected by immunochromatography, acute physiology chronic health evaluation(APACHE Ⅱ)score and sequential organ failure assessment(SOFA) score were performed, the correlation between serum level of Netrin-1 and NSE, S100 β, APACHE Ⅱ and SOFA scores were analyzed by Pearson analysis, and the predictive value of serum Netrin-1 for SAE was analyzed by receiver operating characteristic(ROC) curve. Results SAE patients stayed in ICU for 8.72±1.81days,APACHE Ⅱ 20.10±6.46 points and SOFA 11.57±4.83 points,and they were all significantly higher than the control group ICU time 4.52±1.34 days, APACHE Ⅱ 14.20±5.31 points and SOFA 8.41±3.56 points,the differences were statistically significant(t=4.794~16.971, all P < 0.001).The serum Netrin-1 level of SAE patients was 114.57±30.21 ng/ml, which was significantly lower than that of the control group(162.81±35.43 ng/ml), and the NSE level and the S100β expression level were 9.62±1.76 ng/ml and 1.03± 0.32 μg/ml,respectively,with significantly higher than the control group(7.32±1.35 ng/ml and 0.75±0.21 μg/ml), the differences were statistically significant(t=6.723~9.408, all P < 0.001). The serum Netrin-1level of SAE patients in the death group was 93.78±25.62 ng/ml, which was significantly lower than that of the survival group(134.26±28.05 ng/ml), and NSE,S100β, APACHE Ⅱ and SOFA were 13.01±1.81 ng/ml vs 7.23±1.14 ng/ml,1.29±0.35μg/ml vs 0.81±0.19μg/ml, 22.15±6.21 vs 18.23±5.64 points and 13.25±3.42 vs 10.45±2.95 scores,with significantly higher than the control group,the differences were statistically significant(t=2.708~15.7827, all P < 0.05).The results of correlation analysis showed that the level of serum Netrin-1 was negatively correlated with NSE, S100 β, APACHE Ⅱand SOFA scores(r=-0.451,-0.503,-0.514,-0.409, all P<0.001). The sensitivity, the specificity and the area under the curve of serum Netrin-1 combined with NSE and S100β to predict the risk of brain injury in elderly patients with sepsis were 95.52%and 89.47%(AUC=0.969,95%CI:0.942~0.996, P < 0.001),respectively. The combined diagnosis was better than the detection of serum Netrin-1 alone(AUC=0.873,95%CI=0.819~0.928, P < 0.001). Conclusion The expression level of serum Netrin-1 in elderly SAE patients decreased.Serum Netrin-1 alone or in combination with NSE and S100β have a certain value in predicting the risk of brain injury in elderly patients with sepsis, and has certain clinical application significance.