目的 研究新生儿窒息后血浆褪黑素(MT)、糖皮质激素(GC)水平及褪黑素受体1(MR 1)、糖皮质激素受体α(GRα)表达的变化.方法 选择2014年5月至2015年12月住院的足月窒息新生儿,其中轻度窒息组22例、重度窒息组28例;另选同时期因感染、黄疸等单一病种住院的非窒息足月新生儿50例为对照组.入组新生儿均在出生后24 h内及生后第7天采集外周血,留取血浆及单个核细胞,采用ELISA方法检测血浆MT及GC水平,Real-time PCR检测MR 1、GRα mRNA表达量.结果 生后24 h内,轻度和重度窒息组血浆GC浓度均明显高于对照组;重度窒息组高于轻度组,差异均有统计学意义(P<0.05).生后第7天,轻度和重度窒息组的血浆GC浓度下降,与生后24 h内的差异均有统计学意义(P<0.05),但重度窒息组仍高于轻度组,轻度和重度窒息组均高于对照组,差异有统计学意义(P<0.05).生后24 h内,重度窒息组的血浆MT浓度低于轻度窒息组和对照组,差异均有统计学意义(P<0.05).第7天时,重度和轻度窒息组的血浆MT浓度均高于对照组,与生后24 h内的的差异有统计学意义(P<0.05).生后24 h内重度窒息组GRα mRNA表达水平降低,而轻度窒息组升高,三组间两两比较差异均有统计学意义(P<0.05).第7天,轻度和重度窒息组GRα表达水平均恢复,与对照组的差异无统计学意义(P>0.05).与生后24 h相比较,重度窒息组第7天MR 1 mRNA表达水平高于对照组和轻度窒息组,差异有统计学意义(P<0.05).结论 重度窒息产生的应激反应超过了新生儿的适应范围,MR 1及内源性MT呈高表达状态.%Objective To explore the changes in plasma melatonin (MT) and glucocorticoid (GC) and the expressions of melatonin receptor 1 (MR1) and glucocorticoid receptor alpha (GR alpha) after neonatal asphyxia. Methods Full-term asphyxia neonates (22 cases of mild asphyxia, 28 cases of severe asphyxia) hospitalized from May 2014 to December 2015 were selected. Another 50 non-asphyxiated full-term newborns hospitalized with single disease such as infection and jaundice at the same time were selected as the control group. Peripheral blood samples were collected within 24 hours after birth and 7 days after birth, and plasma and mononuclear cells were separated. The plasma MT and GC expression levels were detected by ELISA. Real-time PCR was used to detect MR1 and GRα mRNA expression. Results The plasma GC concentrations in mild and severe asphyxia group increased significantly within 24 hours after birth, higher than that in control group. In addition, the plasma GC concentration in severe asphyxia group was significantly higher than that in mild group (P<0.05). The concentration of plasma GC in mild and severe asphyxia group decreased on the 7th day after birth (P<0.05) and was significantly lower than that at 24 hours after birth, but it was still higher in the severe asphyxia group than that in mild group; both the mild and severe asphyxia group had higher GC level than that in control group; the differences are statistically significant (P<0.05). Within 24 hours after birth, the plasma MT concentration in severe asphyxia group was lower than that in mild asphyxia group and control group, and there were significant differences (P<0.05). Compared with 24 hours after birth, the concentrations of plasma MT in severe and mild asphyxia groups increased significantly, higher than that in control group on the 7th day, and there were significant differences (P<0.05). The level of GR alpha mRNA expression decreased within 24 hours after birth in severe asphyxia group, but was increased in the mild asphyxia group, and there were significant differences among the three groups (P<0.05). The expression levels of GRα in both mild and severe asphyxia groups recovered on the 7th days after birth, and there were no significant differences compared with control group (P>0.05). Compared with 24 hours after birth , the expression level of MR1 mRNA in severe asphyxia group increased on the 7th day after birth, higher than that in control group and in mild asphyxia group, and there were significant differences (P<0.05). Conclusions The stress caused by severe asphyxia exceeds the adaptation range in the newborn, and results in the high expressions of MR1 and endogenous MT.
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