职业性一氧化碳中毒患者相关血液标志物的动态研究

The dynamic study of related blood markers in patients with occupational carbon monoxide poisoning

目的探讨职业性急性一氧化碳(CO)中毒患者急性中毒期、假愈期和迟发性脑病期血清中Tau蛋白、泛素羧基末端水解酶L1(UCH-L1)、脑源性神经营养因子(BDNF)的动态变化及临床意义。方法选取2018年11月至2021年8月在黑龙江省第二医院神经内科住院治疗的39例职业性急性CO中毒后发生迟发性脑病患者为实验组,并根据病程不同分为急性中毒期、假愈期和迟发性脑病期。根据纳入和排除标准在正常人群中选择39人作为本次研究的对照组。记录实验组及对照组的人群资料;量表测量神经功能缺损评分;采用ELISA法检测并观察比较各组患者血清中Tau蛋白、UCH-L1、BDNF含量;利用ROC分析方法探索相关血液标志物对CO中毒脑病进展情况的诊断功效。结果实验组与对照组一般人群资料比较,无统计学差异,对照组神经功能缺损评分[(1.77±1.59)分]明显低于实验组各期评分[(32.47±3.56)、(27.72±6.63)、(39.25±13.1)分](F=7.779,P<0.01);实验组各期Tau蛋白含量分别为[(235.16±13.06),(179.11±18.98),(140.62±21.37)pg/ml],UCH-L1含量分别为[(46.22±4.32),(25.56±3.66),(29.9±3.47)ng/ml],两者均明显高于对照组的Tau蛋白含量[(76.52±7.71)pg/ml](F=169.993,P<0.01)和UCH-L1含量[(15.28±0.73)ng/ml](F=189.451,P<0.01);实验组各期的BDNF含量分别为[(13.37±4.27),(27.11±5.8),(34.39±4.78)ng/ml],均明显低于对照组[(42.26±2.97)ng/ml](F=159.032,P<0.01);实验组中各期比较显示,迟发性脑病期所检三项蛋白含量[Tau蛋白含量(140.62±21.3)pg/ml,UCH-L1含量(29.9±3.47)ng/ml,BDNF含量(34.39±4.78)ng/ml]与急性中毒期[Tau蛋白含量(235.16±13.06)pg/ml,UCH-L1含量(46.22±4.32)ng/ml,BDNF含量(13.37±4.27)ng/ml]比较,差异均有统计学意义(t=183.65,177.51,168.46,P<0.05),其中Tau蛋白及UCH-L1含量随病情进展呈下降趋势,BDNF含量随病情进展呈上升趋势;诊断CO中毒性脑病进展情况的AUC值,Tau蛋白为0.7851、UCH-L1为0.8395、BDNF为0.7619,三项指标联合为0.8633。结论Tau蛋白、UCH-L1、BDNF三项指标均在CO中毒后出现明显变化,这提示三项指标对早期CO中毒所致脑损伤具有潜在临床评估价值。

Objective To investigate the serum tau protein,ubiquitin carboxy-terminal hydrolase L1(UCH-L1),brain-derived neurotrophic factor in acute poisoning period,pseudo-recovery period and delayed encephalopathy period after acute carbon monoxide(CO)poisoning in occupational environment,and to 1’study the dynamic changes and clinical significance of them.Methods Thirty-nine patients with delayed encephalopathy after occupational acute CO poisoning who were hospitalized in the Department of Neurology,Second Hospital of Heilongjiang Province from November 2018 to August 2021 were selected as the experimental group,and were divided into acute poisoning period,false period convalescent and delayed encephalopathy.According to the inclusion and exclusion criteria,39 people in the normal population were selected as the control group for this study.The population data of the experimental group and the control group were recorded;the neurological deficit score was measured by the scale;the serum Tau protein,UCH-L1 and BDNF levels of the patients in each group were detected by ELISA;exploring the diagnostic efficacy of related blood markers for the progression of CO poisoning encephalopathy by ROC analysis.Results There was no statistical difference in the general population data between the experimental group and the control group,and the neurological deficit score of the control group[(1.77±1.59)points]was significantly lower than that of the experimental group[(32.47±3.56),(27.72±6.63),(39.25±13.1)points](F=7.779,P<0.01);The Tau protein content in the experimental group at each stage was[(235.16±13.06),(179.11±18.98),(140.62±21.37)pg/ml],UCH-L1 contents were[(46.22±4.32),(25.56±3.66),(29.9±3.47)ng/ml],the Tau protein content in the experimental group at each stage was significantly higher than that of the control group[(76.52±7.71)pg/ml](F=169.993,P<0.01),and the UCH-L1 content in the experimental group at each period was also evidently higher than the UCH-L1 content[(15.28±0.73)ng/ml](F=189.451,P<0.01);the BDNF content of the experimental group at each stage was[(13.37±4.27),(27.11±5.8),(34.39±4.78)ng/ml],which were significantly lower than the control group[(42.26±2.97)ng/ml](F=159.032,P<0.01);In the experimental group,the content of three proteins detected in the stage of delayed encephalopathy[Tau protein content(140.62±21.3)pg/ml,UCH-L1 content(29.9±3.47)ngng/ml,BDNF content(34.39±4.78)ng/ml)]was compared with that in acute poisoning stage[Tau protein content(235.16±13.06)pg/ml,UCH-L1 content(46.22±4.32)ng/ml,BDNF content(13.37±4.27)ng/ml],the differences were statistically significant(t=183.65,177.51,168.46,P<0.05),among which the contents of Tau protein and UCH-L1 decreased with the progression of the disease,and the contents of BDNF increased with the progression of the disease.The progression of the disease showed an upward trend;the AUC values for diagnosing the progression of CO toxic encephalopathy were 0.7851 for Tau protein,0.8395 for UCH-L1,0.7619 for BDNF,and 0.8633 for the combination of the three indicators.Conclusion The three indexes of Tau protein,UCH-L1 and BDNF all showed significant changes after CO poisoning,which suggested that the three indexes have potential clinical evaluation value for brain damage caused by early CO poisoning.