摘要
目的探讨急性呼吸窘迫综合征(ARDS)患儿血清褪黑素(Melatonin)、巨噬细胞炎性蛋白-1α(MIP-1α)与核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体和预后的关系。方法选取2021年1月至2023年1月该院收治的ARDS患儿140例纳入ARDS组,另选取同期100例体检健康儿童纳入对照组。根据入院28 d临床结局将ARDS患儿分为死亡组29例和存活组111例。采用酶联免疫吸附试验检测血清Melatonin、MIP-1α、白细胞介素(IL)-1β、IL-18水平,实时荧光定量PCR检测NLRP3 mRNA、半胱氨酸蛋白酶-1(Caspase-1)mRNA水平。采用Pearson相关分析ARDS患儿血清Melatonin、MIP-1α水平与NLRP3炎症小体相关指标(NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18)的相关性。采用多因素Cox回归分析影响ARDS患儿预后的因素。根据ARDS患儿血清Melatonin、MIP-1α水平均值分为高/低血清Melatonin、MIP-1α组,Kaplan-Meier法绘制高/低血清Melatonin、MIP-1α水平ARDS患儿生存曲线。采用受试者工作特征(ROC)曲线分析血清Melatonin、MIP-1α对ARDS患儿死亡的预测价值。结果与对照组比较,ARDS组血清Melatonin水平降低,血清MIP-1α、IL-1β、IL-18和外周血单核细胞NLRP3 mRNA、Caspase-1 mRNA水平升高(P<0.05)。Pearson相关分析显示,ARDS患儿血清Melatonin水平与NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18均呈负相关(P<0.05),MIP-1α水平与NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18均呈正相关(P<0.05)。多因素Cox回归分析显示,急性生理学和慢性健康状况评价Ⅱ评分、NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18、MIP-1α为影响ARDS患儿预后的独立危险因素,Melatonin为独立保护因素(P<0.05)。Kaplan-Meier生存曲线分析显示,高血清Melatonin组28 d生存率高于低血清Melatonin组(P<0.05),高血清MIP-1α组28 d生存率低于低血清MIP-1α组(P<0.05)。ROC曲线分析显示,血清Melatonin、MIP-1α联合预测ARDS患儿死亡的曲线下面积为0.881(95%CI 0.816~0.930),大于血清Melatonin、MIP-1α单独预测的0.785(95%CI 0.708~0.850)、0.778(95%CI 0.700~0.844)。结论ARDS患儿血清Melatonin水平降低、MIP-1α水平升高,与NLRP3炎症小体和预后密切相关,联合检测血清Melatonin、MIP-1α水平对ARDS患儿预后具有较高的预测价值。
Objective To study the relationship between serum Melatonin,macrophage inflammatory protein-1α(MIP-1α)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome and prognosis in children with acute respiratory distress syndrome(ARDS).Methods A total of 140 children with ARDS who were admitted to the hospital from January 2021 to January 2023 were enrolled as the ARDS group,and 100 healthy children who underwent physical examination during the same period were enrolled as the control group.According to the clinical outcome on 28 d after admission,the children with ARDS were divided into a death group(29 cases)and a survival group(111 cases).Enzyme-linked immunosorbent assay was used to detect the serum levels of Melatonin,MIP-1α,interleukin(IL)-1β,and IL-18.Real-time fluorescent quantitative PCR was used to detect the mRNA levels of NLRP3 and Caspase-1.Pearson correlation was used to analyze the correlation between serum levels of Melatonin and MIP-1αand NLRP3 inflammasome related indicators(NLRP3 mRNA,Caspase-1 mRNA,IL-1β,IL-18)in children with ARDS.Multivariate Cox regression analysis was used to analyze the factors affecting the prognosis of children with ARDS.According to the mean levels of serum Melatonin and MIP-1α,the children with ARDS were divided into a high/low Melatonin group and MIP-1αgroup.The Kaplan-Meier method was used to draw the survival curves of ARDS children with high/low levels of serum Melatonin and MIP-1α.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum Melatonin and MIP-1αfor death in children with ARDS.Results Compared with the control group,the ARDS group had a significantly decreased serum Melatonin level and significantly increased serum MIP-1α,IL-1β,IL-18 and NLRP3 mRNA and Caspase-1 mRNA levels in peripheral blood mononuclear cells(P<0.05).Pearson correlation analysis showed that the serum Melatonin level of ARDS children was negatively correlated with NLRP3 mRNA,Caspase-1 mRNA,IL-1βand IL-18(P<0.05),the level of MIP-1αwas positively correlated with NLRP3 mRNA,Caspase-1 mRNA,IL-1βand IL-18(P<0.05).Multivariate Cox regression analysis showed that acute physiology and chronic health evaluationⅡscore,NLRP3 mRNA,Caspase-1 mRNA,IL-1β,IL-18 and MIP-1αwere independent risk factors affecting the prognosis of children with ARDS.Melatonin was an independent protective factor(P<0.05).Kaplan-Meier survival curve analysis showed that the 28 d survival rate in high Melatonin group was higher than that in low Melatonin group(P<0.05),and the 28 d survival rate in high MIP-1αgroup was lower than that in low MIP-1αgroup(P<0.05).ROC curve analysis showed that the area under the curve of Melatonin and MIP-1αcombined to predict the death of ARDS children was 0.881(95%CI 0.816—0.930).It was higher than 0.785(95%CI 0.708—0.850)and 0.778(95%CI 0.700—0.844)predicted by Melatonin or MIP-1αalone.Conclusion The serum Melatonin level is decreased and MIP-1αlevel is increased in children with ARDS,which is closely related to NLRP3 inflammasome and prognosis.Combined detection of serum Melatonin and MIP-1αlevels has a high predictive value for the prognosis of children with ARDS.
作者
余娟
王俭
杜华伟
杨学琴
杨婕
YU Juan;WANG Jian;DU Huawei;YANG Xueqin;YANG Jie(Department of Pediatrics,Meishan People′s Hospital,Meishan,Sichuan 620010,China;Department of Neonatology,Meishan People′s Hospital,Meishan,Sichuan 620010,China)
出处
《国际检验医学杂志》
CAS
2024年第11期1331-1337,共7页
International Journal of Laboratory Medicine
基金
2019年第二批四川省卫生健康科研课题普及项目(19PJ1205)。
