腰椎脊柱爆裂性骨折伴急性脊髓损伤患者血清NFL、HSP70、NSE表达与神经功能的关系

Relationship between the expressions of serum NFL,HSP70,NSE and neurological function in lumbar burst fracture patients with acute spinal cord injury

目的研究腰椎脊柱爆裂性骨折伴急性脊髓损伤(SCI)患者血清神经丝轻链(NFL)、热休克蛋白70(HSP70)、神经元特异性稀醇化酶(NSE)表达与神经功能的关系。方法前瞻性选取2018年1月—2020年4月期间空军军医大学第一附属医院骨科收治的113例脊柱爆裂性骨折患者,均为腰椎爆裂性骨折,根据美国脊髓损伤协会(ASIA)神经功能分级法,分为完全SCI组34例,不完全SCI组79例;男性51例,女性62例;年龄45~66岁,平均55.7岁;道路交通伤94例,高处坠落伤19例;糖尿病7例,冠心病4例,高血压病7例;饮酒史23例、吸烟史17例。同时纳入同期在笔者医院行身体检查的60例健康志愿者为对照组,比较三组受试者治疗前血清NFL、HSP70和NSE水平。患者均行后路长节段椎弓根螺钉固定术,随访6个月后,根据神经功能恢复情况,将患者分成预后良好组(72例)和预后不良组(41例)。单因素分析两组患者基线资料,对差异有统计学意义的单因素进行Logistic多因素回归分析,探究脊柱爆裂性骨折患者预后的独立影响因素,并应用受试者工作特征(ROC)曲线评估血清指标与神经功能的关系。结果完全SCI组、不完全SCI组和对照组受试者血清NFL(67.4±6.7)pg/mL vs.(29.3±6.4)pg/mL vs.(6.0±1.5)pg/mL,F=58.304,P<0.001、HSP70(26.6±4.9)ng/mL vs.(19.2±4.6)ng/mL vs.(13.2±3.4)ng/mL,F=13.633,P<0.001和NSE(24.9±3.0)ng/mL vs.(14.7±3.6)ng/mL vs.(10.2±3.0)ng/mL,F=10.431,P<0.001差异有统计学意义。随访6个月,预后不良组血清NFL(59.2±7.0)pg/mL vs.(18.3±4.0)pg/mL,t=34.416,P<0.001、HSP70(20.3±3.1)ng/mL vs.(15.3±3.3)ng/mL,t=7.937,P<0.001和NSE(21.0±4.1)ng/mL vs.(12.8±3.0)ng/mL,t=11.385,P<0.001表达明显高于预后良好组。Logistic结果表明血清NFL(OR=2.776,95%CI2.238~3.444)、血清HSP70(OR=2.998,95%CI1.513~5.942)和血清NSE(OR=1.879,95%CI1.219~2.898)等指标是爆裂性骨折合并SCI患者预后不良的独立影响因素(P<0.05)。根据ROC曲线可得,血清NFL诊断的临界值为40.39pg/mL,其对应的敏感度为73.17%,特异度为73.61%,曲线下面积(AUC)为0.801(95%CI0.750~0.852);血清HSP70诊断的临界值为17.33ng/mL,其对应的敏感度为70.73%,特异度为69.44%,AUC为0.760(95%CI0.707~0.812);血清NSE诊断的临界值为16.03ng/mL,其对应的敏感度为58.54%,特异度为58.33%,AUC为0.631(95%CI0.564~0.698)。将回归预测方程作为新变量P,在最佳临界切点时,回归分析的敏感度为80.49%,特异度为79.17%,AUC为0.869(95%CI0.831~0.907),有一定的预测价值。结论血清NFL、HSP70和NSE在脊柱爆裂性骨折合并SCI患者异常高表达,且上述诸血清因子是患者神经功能预后不良的独立危险因素。

Objective To study the relationship between the expressions of serum nerve filament light chain(NFL),heat shock protein 70(HSP70),neuron-specific enolase(NSE)and neurological function in spinal burst fracture patients with acute spinal cord injury(SCI).Methods A total of 113 patients with spinal burst fractures admitted to our hospital from Jan.2018 to Apr.2020 were prospectively selected,including 34 cases of complete SCI and 79 cases of incomplete SCI;there were 51 males and 62 females;their age range was 45-66 years,with an average age of 55.7 years;19 cases of high falls and 94 cases of road traffic injuries;7 cases of diabetes,4 cases of coronary heart disease and 7 cases of hypertension;23 cases had drinking history and 17 cases had smoking history.Another 60 healthy volunteers who underwent physical examination in our hospital in the same period were selected as the control group.The serum levels of NFL,HSP70 and NSE were compared among the three groups.After 6 months of follow-up,the patients were divided into two groups according to the recovery of neurological function:good prognosis group(n=72)and poor prognosis group(n=41).The baseline data of the two groups were analyzed by univariate analysis.Logistic multivariate regression analysis was used to explore the independent prognostic factors of patients with spinal burst fracture,and the relationship between serum indexes and neurological function was evaluated by ROC curve.Results Serum NFL[(67.4±6.7)pg/mL vs.(29.3±6.4)pg/mL vs.(6.0±1.5)pg/mL,F=58.304,P<0.001],HSP70[(26.6±4.9)ng/mL vs.(19.2±4.6)ng/mL vs.(13.2±3.4)ng/mL,F=13.633,P<0.001]and NSE[(24.9±3.0)ng/mL vs.(14.7±3.6)ng/mL vs.(10.2±3.0)ng/mL,F=10.431,P<0.001]among complete SCI group,incomplete SCI group and control group showed statistically significant differences.During the 6-month follow-up,serum NFL[(59.2±7.0)pg/mL vs.(18.3±4.0)pg/mL,t=34.416,P<0.001]and HSP70[(20.3±3.1)ng/mL vs.(15.3±3.3)ng/mL,t=7.937,P<0.001]and NSE[(21.0±4.1)ng/mL vs.(12.8±3.0)ng/mL,t=11.385,P<0.001]in the poor prognosis group were significantly higher than those in the good prognosis group.Logistic results showed that serum NFL(OR=2.776,95%CI:2.238-3.444),serum HSP70(OR=2.998,95%CI:1.513-5.942)and serum NSE(OR=1.879,95%CI:1.219-2.898)were independent factors affecting the poor prognosis of burst fracture patients with SCI.According to the ROC curve,the critical value of serum NFL diagnosis was 40.39pg/mL,the corresponding sensitivity,specificity and AUC were 73.17%,73.61%and 0.801(95%CI:0.750-0.852),respectively;the critical value of serum HSP70 was 17.33ng/mL,and the corresponding sensitivity,specificity and AUC were 70.73%,69.44%and 0.760(95%CI:0.707-0.812),respectively;the critical value of serum NSE diagnosis was 16.03 ng/mL,and the corresponding sensitivity,specificity and AUC were 58.54%,58.33%,and 0.631(95%CI:0.564-0.698).Taking the regression prediction equation as a new variable P,at the optimal critical tangent point,the sensitivity of regression analysis was 80.49%,the specificity was 79.17%,and the AUC was 0.869(95%CI:0.831-0.907),which had a certain predictive value.Conclusion Serum NFL,HSP70 and NSE are abnormally highly expressed in patients with spinal burst fracture complicated with SCI,and these serum factors are independent risk factors for poor prognosis.