血清血脑屏障标志物水平与创伤性脑损伤患儿病情严重程度及预后的相关性分析

Correlation between levels of serum blood-brain barrier markers and disease severity,prognosis of children with traumatic brain injury

目的 探讨并分析血清血脑屏障标志物水平与创伤性脑损伤(TBI)患儿病情程度及预后的相关性。方法 选取2019年5月至2022年8月徐州市儿童医院收治的TBI患儿92例,根据入院时格拉斯哥昏迷指数(GCS)评分将其分为轻度组(28例,13~15分)、中度组(39例,9~12分)和重度组(25例,3~8分)。另选取同期该院因诊断需要行腰椎穿刺检查而脑脊液结果正常的患儿46例作为对照组。比较各组血清S100钙化蛋白B(S100B)、神经元特异性烯醇化酶(NSE)、紧密连接蛋白(Occludin)、紧密连接蛋白(claudin)-5、水通道蛋白(AQP)-4、胶质纤维酸性蛋白(GFAP)、基质金属蛋白酶(MMP)-9表达水平。采用Spearman相关性分析上述指标与病情严重程度的关系。采用格拉斯哥预后量表(GOS)评分评估随访6个月后患儿预后情况,比较不同预后患儿的血清血脑屏障标志物水平,采用受试者工作特征(ROC)曲线评价上述指标对TBI患儿预后的预测价值。结果 轻度组、中度组和重度组血清NSE、AQP-4、GFAP、MMP-9和Occludin水平均高于对照组,血清claudin-5水平低于对照组(P<0.05);重度组血清NSE、AQP-4、GFAP、MMP-9和Occludin水平高于轻、中度组(P<0.05),血清claudin-5水平低于轻、中度组(P<0.05);中度组和重度组血清S100B水平高于对照组和轻度组(P<0.05),重度组血清S100B水平高于中度组(P<0.05),但轻度组和对照组比较差异无统计学意义(P>0.05)。Spearman等级相关性显示,疾病严重程度均与血清S100B、NSE、AQP-4、GFAP、MMP-9、Occludin水平呈正相关(r=0.221、0.215、0.328、0.335、0.344、0.222,均P<0.05),与claudin-5呈负相关(r=-0.371,P<0.05)。随访6个月,预后良好组血清S100B、NSE、AQP-4、GFAP、MMP-9、Occludin水平均低于预后不良组(P<0.05),claudin-5水平高于预后不良组(P<0.05)。ROC曲线分析结果显示,血清S100B、NSE、AQP-4、GFAP、MMP-9、claudin-5、Occludin及联合检测预测TBI患儿预后的曲线下面积(AUC)分别为0.798、0.756、0.779、0.781、0.765、0.785、0.777和0.923,均具有较高的诊断价值。结论 血清S100B、NSE、AQP-4、GFAP、MMP-9、claudin-5、Occludin可能参与了TBI患儿病情的发展,可为TBI患儿预后评估的辅助指标。

Objective To explore and analyze the correlation between levels of serum blood-brain barrier markers and disease severity,prognosis of children with traumatic brain injury(TBI).Methods A total of 92 children with TBI admitted to the hospital were enrolled between May 2019 and August 2022.According to score of Glasgow Coma Scale(GCS)score at admission,they were divided into mild group(28 cases,13-15 points),moderate group(39 cases,9-12 points)and severe group(25 cases,3-8 points).In addition,46 children with normal cerebrospinal fluid results due to lumbar puncture were selected as the control group.The expression levels of serum S100 calcified protein B(S100B),neuron specific enolase(NSE),Occludin,tight junction protein(claudin)-5,aquaporin(AQP)-4,glial fibrillary acid protein(GFAP)and matrix metalloproteinase(MMP)-9 in different groups were compared.Spearman correlation was used to analyze the relationship between the above indexes and the severity of the disease.Glasgow Prognosis Scale(GOS)score was used to evaluate the prognosis of children with TBI after 6 months of follow-up.Serum blood-brain barrier marker levels of children with different prognosis were compared,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of the above indicators for the prognosis of children with TBI.Results Serum NSE,AQP-4,GFAP,MMP-9 and Occludin levels in mild,moderate and severe groups were higher than those in control group,while serum claudin-5 levels were lower than those in control group(P<0.05).The serum NSE,AQP-4,GFAP,MMP-9 and Occludin levels in severe group were higher than those in light and moderate group(P<0.05),and serum claudin-5 levels were lower than those in light and moderate group(P<0.05).Serum S100B levels in moderate group and severe group were higher than that in control group and mild group(P<0.05),serum S100B level in severe group was higher than that in moderate group(P<0.05),but there was no statistical significance between mild group and control group(P>0.05).Spearman grade correlation analysis showed that disease severity was positively correlated with serum S100B,NSE,AQP-4,GFAP,MMP-9 and Occludin levels(r=0.221,0.215,0.328,0.335,0.344,0.222,all P<0.05),and negatively correlation with claudin-5(r=-0.371,P<0.05).After 6 months of follow-up,serum S100B,NSE,AQP-4,GFAP,MMP-9 and Occludin levels in the good prognosis group were lower than those in the poor prognosis group(P<0.05),and claudin-5 levels were higher than those in the poor prognosis group(P<0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum S100B,NSE,AQP-4,GFAP,MMP-9,claudin-5,Occludin and the combined detection for predicting the prognosis of TBI children were 0.798,0.756,0.779,0.781,0.765,0.785,0.777 and 0.923,respectively,all had high diagnostic value.Conclusion Serum S100B,NSE,AQP-4,GFAP,MMP-9,claudin-5 and Occludin may participate in disease development of TBI children,which can be applied as auxiliary indexes for prognosis evaluation.