新生儿缺氧缺血性脑病患儿血清中lncRNA H19和miR-19a的表达及临床意义

Expressions and clinical significance of lncRNA H19 and miR-19a in serum of neonates with neonatal hypoxic-ischemic encephalopathy

摘要

目的 探讨新生儿缺氧缺血性脑病(HIE)患儿血清中长链非编码RNA H19(lncRNA H19)和miR-19a的表达情况及临床意义。方法 选取2017年2月至2019年9月邯郸市中心医院收治的93例HIE患儿为研究对象(HIE组),根据HIE严重程度将患儿分为轻症组48例、中症组29例和重症组16例,选择同期在院健康新生儿85例为对照组;采用实时荧光定量PCR(qRT-PCR)法检测血清lncRNA H19和miR-19a水平,并进行新生儿神经行为评分(NBNA);采用Pearson相关性分析患儿血清lncRNA H19和miR-19a的相关性,以及二者分别与NBNA评分的关系.对患儿进行两年的随访,根据随访结果将其分为预后良好组72例与预后不良组21例;再根据血清lncRNA H19、miR-19a水平的平均值将其分为高表达和低表达,分析血清lncRNA H19和miR-19a水平与HIE患儿预后的关系。结果 HIE组患儿血清lncRNA H19水平明显高于对照组,而miR-19a水平明显低于对照组,经比较差异均具有统计学意义(t值分别为22.144、21.842,P<0.05).轻度组、中度组、重度组HIE患儿血清lncRNA H19和miR-19a水平及NBNA评分比较,差异均有统计学意义(F值分别为38.363、131.168、136.265,P<0.05).lncRNA H19与miR-19a存在结合位点;Pearson相关性分析显示,HIE患儿血清lncRNA H19与miR-19a水平呈显著负相关(r=-0.524,P=0.000).HIE患儿血清lncRNA H19水平与NBNA评分呈显著负相关(r=-0.608,P=0.000),miR-19a水平与NBNA评分呈显著正相关(r=0.535,P=0.000).HIE患儿血清lncRNA H19高表达的预后良好率明显低于低表达,血清miR-19a高表达的预后良好率明显高于低表达,经比较差异均有统计学意义(χ²值分别为6.561、4.736,P<0.05)。结论 新生儿HIE患儿的血清lncRNA H19和miR-19a水平呈异常表达,其水平与NBNA评分相关,二者可反映HIE患儿疾病严重程度及预后情况.

Abstract

Objective To explore expressions of long non-coding RNA H19 (lncRNA H19) and microRNA-19a (miR-19a) in serum of neonates with hypoxic ischemic encephalopathy (HIE) and their clinical significance. Methods A total of 93 neonates with HIE who admitted to Handan Municipal Central Hospital from February 2017 to September 2019 were selected as research subjects. According to severity of HIE, the neonates were divided into three groups: mild HIE group (48 cases), moderate HIE group (29 cases) and severe HIE group (16 cases). 85 healthy neonates in our hospital in the same period were selected as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was applied to detect serum lncRNA H19 and miR-19a levels. Neonatal Behavior Neurological Assessment (NBNA) was performed on all neonates. Pearson correlation analysis was used to analyze correlations between serum lncRNA H19 and miR-19a levels, and relationship between the two indexes and the NBNA scores. Results Compared with the control group, the serum lncRNA H19 level of the neonates in the HIE group was higher, while the miR-19a level was lower, and the differences were significant (t=22.144 and 21.842 respectively, both P<0.05). Moreover, the serum lncRNA H19 level elevated with increase in severity of HIE, and the serum miR-19a level and NBNA score lowered with decrease in severity of HIE (all P<0.05). There were significant differences in serum expression levels of lncRNA H19 and miR-19a and NBNA scores among the mild HIE group, the moderate HIE group and the severe HIE group (F=38.363, 131.168 and 136.265 respectively, all P<0.05). The bioinformatics website ENCORI showed that lncRNA H19 and miR-19a had common binding sites. Pearson correlation analysis shown that the serum lncRNA H19 level was negatively correlated with the serum miR-19a level and NBNA scores (r=-0.524 and -0.608 respectively, both P=0.000), while the serum miR-19a level was positively correlated with NBNA scores (r=0.535, P=0.000). The good prognosis rate of these neonates in the high lncRNA H19 expression group was significantly lower than that in the low lncRNA H19 expression group, and the good prognosis rate of these neonates in the high miR-19a expression group was significantly higher than that in the low miR-19a expression group, the differences were both significant (χ²=6.561 and 4.736 respectively, both P<0.05). Conclusion LncRNA H19 and miR-19a abnormally expressed in the neonates with HIE, and their serum expression levels are related to NBNA scores. The expression levels of lncRNA H19 and miR-19a in serum can reflect severity of the disease and prognosis of the neonates with HIE.

关键词

新生儿 / 缺氧缺血性脑病 / 长链非编码RNA H19 / 微小RNA-19a / 神经行为评分

Key words

neonate / hypoxic-ischemic encephalopathy / long non-coding RNA H19 / microRNA-19a / behavior neurological assessment

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基金资助

河北省重点研发计划自筹项目(182777236)