血清Nox2、ATG7水平对新生儿窒息心肌损伤的评估价值

Serum Nox2 and ATG7 levels for assessing myocardial injury in neonates with asphyxia

目的探讨自噬相关基因-7(ATG7)、烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(Nox2)在新生儿窒息病儿血清中的表达及早期诊断价值。方法选取2019年1月至2021年12月在郑州大学第三附属医院产科分娩的75例新生儿窒息病儿为研究组,根据是否合并心肌损伤将病儿分为窒息心肌损伤组31例,窒息非心肌损伤组44例。同期选择50例健康足月新生儿为对照组。收集一般资料,采用酶联免疫吸附测定(ELISA)测量血清ATG7水平,采用蛋白质印迹法检测Nox2水平,以Nox2/β肌动蛋白的灰度比值为Nox2表达量;采用Pearson法分析ATG7、Nox2表达的相关性及与各指标的相关性;利用受试者操作特征曲线(ROC曲线)评价Nox2、ATG7水平对新生儿窒息心肌损伤的诊断价值。结果与对照组[0.26±0.06、(4.83±0.61)ng/L]比较,新生儿窒息病儿血清Nox2(0.65±0.09)、ATG7[(21.04±3.66)ng/L]表达水平升高,且窒息心肌损伤组[0.85±0.11、(24.23±3.98)ng/L]病儿血清中Nox2、ATG7水平高于窒息非心肌损伤组[0.51±0.08、(18.80±3.43)ng/L](P<0.05);窒息心肌损伤病儿血清中Nox2、ATG7表达呈显著正相关(r=0.57,P<0.05);病儿血清中Nox2和ATG7表达与肌酸激酶同工酶(CK-MB)、缺血修饰白蛋白(IMA)、超敏C-反应蛋白(hs-CRP)、氨基末端脑钠肽前体(NT-ProBNP)、肌钙蛋白I(cTnI)、肌红蛋白表达均呈正相关(P<0.05);ROC曲线结果显示,血清Nox2、ATG7水平预测新生儿窒息合并心肌损伤的曲线下面积(AUC)及其95%CI分别为0.91(0.82,0.96)、0.89(0.80,0.95),对应的灵敏度分别为83.87%、87.10%,特异度分别为84.09%、75.00%,二者联合预测的AUC及其95%CI为0.92(0.84,0.97),灵敏度为90.32%,特异度为81.82%。结论窒息心肌损伤病儿血清中Nox2、ATG7表达均上调,二者联合检测对窒息心肌损伤有一定的诊断价值。

Objective To investigate the expression and early diagnostic value of autophagy-related gene-7(ATG7)and nicotinamide adenine dinucleotide phosphate oxidase 2(Nox2)in the serum of infants with neonatal asphyxia.Methods Seventy-five cases of as-phyxiated neonates who were delivered at the Department of Obstetrics and Gynecology of the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were selected as the study group,and the infants were divided into 31 cases in the asphyxiated cardiomyopathy injury group and 44 cases in the asphyxiated noncardiomyopathy injury group according to whether they had cardiomyopathy injury.During the same period,50 healthy full-term newborns were selected as the control group.General da-ta were collected,serum ATG7 levels were measured by enzyme-linked immunosorbent assay(ELISA),Nox2 levels were detected by Western blotting,using the grayscale ratio of Nox2/β-actin as the expression level of Nox2;the correlation of ATG7 and Nox2 expres-sion and the correlation with various indices were analyzed by Pearson's method;and the diagnostic value of Nox2 and ATG7 levels for neonatal asphyxiated myocardial injuries were evaluated by using receiver operating characteristic(ROC)curves.Results Compared with those in the control group[0.26±0.06,(4.83±0.61)ng/L],the serum Nox2(0.65±0.09)and ATG7[(21.04±3.66)ng/L]expression levels were elevated in neonatal asphyxiated patients,and the serum levels of Nox2 and ATG7 were greater in the asphyxiated cardiac injury group[0.85±0.11,(24.23±3.98)ng/L]than in the asphyxiated noncardiac injury group[0.51±0.08,(18.80±3.43)ng/L](P<0.05).The levels of Nox2 and ATG7 were greater than those in the asphyxiated nonmyocardial injury group[0.51±0.08,(18.80±3.43)ng/L](P<0.05).There was a significant positive correlation between Nox2 and ATG7 expression in the serum of sick infants with asphyxia-relat-ed myocardial injury(r=0.57,P<0.05).Serum Nox2 and ATG7 expression in sick infants was positively correlated with creatine kinase isoenzyme(CK-MB),ischemia-modified albumin(IMA),ultrasensitive C-reactive protein(hs-CRP),amino-terminal brain natriuretic peptide precursor(NT-ProBNP),troponin I(cTnI),and myoglobin expression(P<0.05).The results of ROC curve revealed that the AUC and 95%CI of serum Nox2 and ATG7 for the prediction of neonatal asphyxia combined with myocardial injury were 0.91(0.82,0.96)and 0.89(0.80,0.95),respectively,which corresponded to sensitivities of 83.87%and 87.10%,respectively,and specificities of 84.09%and 75.00%,respectively.The combination of these two parameters predicted an AUC and its 95%CI of 0.92(0.84,0.97),re-spectively,with a sensitivity of 90.32%and a specificity of 81.82%.Conclusion The expression of Nox2 and ATG7 was increased in the serum of infants with asphyxia-induced myocardial injury,and the combination of these two assays has a certain diagnostic value for asphyxia-induced myocardial injury.