| 曾浩,陈玉霞,司文.围生期缺血缺氧性脑病的微 RNA生物标志物筛选研究[J].安徽医药,2023,27(9):1849-1852. |
| 围生期缺血缺氧性脑病的微 RNA生物标志物筛选研究 |
| Screening of microRNA biomarkers in perinatal ischemic-hypoxic encephalopathy |
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| DOI：10.3969/j.issn.1009-6469.2023.09.034 |
| 中文关键词: 缺氧缺血，脑 微 RNA 生物标志物 新生儿 围生期 |
| 英文关键词: Hypoxia-ischemia, brain MicroRNA Biomarkers Neonatal Perinatal stage |
| 基金项目:深圳市科技创新委员会基础研究项目( JCYJ20190808154015736)；深圳市龙华区医疗卫生机构区级科研项目( 2020191) |
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| 中文摘要: |
| 目的研究围生期缺血缺氧性脑病( HIE)的微 RNA(miRNA)生物标志物的筛选情况。方法通过动态队列研究法获取 2020年 1月至 2021年 1月深圳市龙华区中心医院 144例 HIE病儿作为受试者。将其根据病情严重程度的差异分作轻度 HIE组 42例、中度 HIE组 62例以及重度 HIE组 40例，另取同期该院 50例健康新生儿作为对照组。分别采集所有新生儿脐带血进行测序比较分析差异表达 miRNA，筛选 3个和 HIE相关的 miRNA作为早期预测 HIE的生物标志物，并分析各组新生儿上述 3个 miRNA表达情况的差异。采用 Spearman相关性分析明确 HIE病情严重程度和 miRNA表达的关系。此外，将所有 HIE病儿按照是否合并脏器损伤分为合并脏器损伤组 102例以及未合并脏器损伤组 42例，比较两组上述 3个 miRNA表达情况的差异。此外，检测并比较 HIE组和对照组血清诱导型一氧化氮合酶( iNOS)、内皮素 -1水平。结果 miRNA芯片通过扫描、分析以及标准化处理，结果发现 miRNA芯片共检测 miRNA达 921种。相较于对照组， HIE病儿血浆中有 29种 miRNA表达异常升高， 26种 miRNA表达异常下降，选择差异有统计学意义的 miRNA实施生物学信息分析，发现了 miR-4472、miR-5195-3p以及 miR6794-5p可能具有潜在的预测 HIE作用。重度 HIE组 miR-4472、miR-5195-3p以及 miR-6794-5p表达水平分别为 0.71±0.12、2.34±0.28、2.24±0.24，均高于对照组的 0.20±0.04、0.78±0.15、0.47±0.11和轻度 HIE组的 0.37±0.08、0.92±0.18、0.89±0.15以及中度组的 0.55±0.09、1.45±0.23、1.46±0.20，且轻度 HIE组、中度 HIE组 miR-4472、miR-5195-3p以及 miR-6794-5p表达水平均高于对照组，中度 HIE组 miR-4472、miR-5195-3p以及 miR-6794-5p表达水平均高于轻度 HIE组(均 P<0.05)。 HIE病儿病情严重程度和 miR-4472、miR-5195-3p、miR-6794-5p表达均呈正相关关系(均 P<0.05)。合并脏器损伤 HIE病儿 miR-4472、miR-5195-3p、 miR-6794-5p表达水平分别为 0.60±0.09、2.05±0.18、1.70±0.31，均高于未合并脏器损伤组的 0.46±0.03、1.58±0.12、1.37±0.23(均 P<0.05)。 HIE组血清 iNOS及内皮素 -1水平均高于对照组(均 P<0.05)。结论 HIE的 miRNA生物标志物包括 miR-4472、miR5195-3p、miR-6794-5p，且上述 miRNA表达水平和病儿病情严重程度以及脏器损伤有关，值得临床重点关注。 |
| 英文摘要: |
| Objective To study the screening of microRNA (miRNA) biomarkers in perinatal ischemic-hypoxic encephalopathy (HIE).Methods A total of 144 HIE infants were obtained as subjects from January 2020 to January 2021 in Shenzhen Longhua Dis-trict Central Hospital by the dynamic cohort study method. According to the severity of the disease, they were divided into a mild HIEgroup (42 cases), a moderate HIE group (62 cases) and a severe HIE group (40 cases), and 50 healthy infants in the same period of timewere selected as the control group. The umbilical cord blood of all neonates was sequenced and analyzed for differentially expressedmiRNAs, three HIE-related miRNAs were screened as biomarkers for the early prediction of HIE, and the differences in the expressionof the above three miRNAs were analyzed in the infants of each group. Spearman correlation analysis was used to clarify the relation-ship between HIE disease severity and miRNA expression. In addition, all HIE infants were divided into 102 cases in the group with or-gan damage and 42 cases in the group without organ damage according to whether they had organ damage, and the differences in the ex-pression of the above three miRNAs between the two groups were compared. In addition, the serum levels of inducible nitric oxide syn-thase (iNOS) and endothelin-1 were measured and compared between the HIE and control group.Results A total of 921 miRNAs were detected by miRNA microarray through scanning, analysis and standardization. Compared with the control group, the plasma expressionof 29 miRNAs was abnormally elevated, and 26 miRNAs were abnormally decreased in HIE patients. Biological information analysiswas performed to select the miRNAs with the most significant differences, and miR-4472, miR-5195-3p, and miR-6794-5p were found to have a potential predictive role in HIE. The expression levels of miR-4472, miR-5195-3p, and miR-6794-5p in the severe HIE groupwere 0.71±0.12, 2.34±0.28, and 2.24±0.24, respectively, which were higher than those in the control group (0.20±0.04, 0.78±0.15,0.47±0.11), the mild HIE group (0.37±0.08, 0.92±0.18, 0.89±0.15) and the moderate group (0.55±0.09, 1.45±0.23, 1.46±0.20). The ex-pression levels of miR-4472, miR-5195-3p, and miR-6794-5p in the mild and moderate HIE groups were higher than those in the con- trol group, and the expression levels of miR-4472, miR-5195-3p, and miR-6794-5p in the moderate HIE group were higher than those in the mild group (all P<0.05). There was a positive correlation between the severity of HIE and the expression of miR-4472, miR-51953p and miR-6794-5p (all P<0.05). The expression levels of miR-4472, miR-5195-3p, and miR-6794-5p in HIE patients with combinedorgan injury were 0.60±0.09, 2.05±0.18, and 1.70±0.31, respectively, which were higher than those in the non combined organ injurygroup (0.46±0.03, 1.58±0.12, 1.37±0.23, all P<0.05). The levels of serum iNOS and endothelin-1 in the HIE group were higher than those in the control group (P<0.05).Conclusion The miRNA biomarkers of HIE include miR-4472, miR-5195-3p and miR-6794-5p,and the expression levels of the above miRNAs are related to the severity of the disease and organ injury in infants, which are worthy ofclinical attention. |
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