新生儿缺氧缺血性脑病脐带血miR-374a-5p、<i>RAB10</i>表达及临床意义

张阵; 卓飞翔; 武玉猛; 陈信

doi:10.16766/j.cnki.issn.1674-4152.003205

新生儿缺氧缺血性脑病脐带血miR-374a-5p、RAB10表达及临床意义

doi: 10.16766/j.cnki.issn.1674-4152.003205

蚌埠医学院第一附属医院儿科，安徽蚌埠 233004

基金项目:

安徽省高校自然科学研究项目 KJ2021A0800

详细信息

通讯作者:
陈信，E-mail：44783939@qq.com

中图分类号: R722
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- 文章访问数: 100
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- 被引次数: 0
出版历程
- 收稿日期: 2022-11-20
- 网络出版日期: 2023-11-23

Expression and clinical significance of miR-374a-5p and RAB10 in cord blood of neonates with hypoxic-ischemic encephalopathy

Department of Pediatrics, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的探讨微小RNA-374a-5p(micro-RNA-374a-5p，miR-374a-5p)、RAB10蛋白在新生儿缺氧缺血性脑病(HIE)患儿脐带血中的表达水平及临床意义。方法选取2020年12月—2022年8月在蚌埠医学院第一附属医院出生的新生儿75例，按照HIE患儿纳入与排除标准及患儿是否发生窒息将其分为围产期窒息组(26例)、HIE组(27例，按照HIE分度指南进行分组，HIE轻度组14例、HIE中度组7例、HIE重度组6例)、健康组22例。患儿均在出生30 min内采集脐带血，采用实时荧光定量(qRT-PCR)检测miR-374a-5p、RAB10蛋白的表达水平。结果各组性别、分娩方式、胎龄、出生体重之间比较差异无统计学意义(均P>0.05)。窒息组、HIE组、健康组miR-374a-5p(F=340.618，P < 0.001)、RAB10 (F=100.906，P < 0.001)比较差异均有统计学意义，其中HIE组新生儿脐带血血清miR-374a-5p表达水平低于健康组，RAB10水平高于健康组，差异均有统计学意义(均P < 0.05)。HIE轻中重度3组miR-374a-5p比较，差异有统计学意义(0.11±0.03、0.08±0.03、0.03±0.01，F=39.403，P < 0.001)，其中中度组miR-374a-5p表达水平低于轻度组，重度组低于轻度组和中度组，差异均有统计学意义(均P < 0.05)。HIE轻中重度3组患儿脐带血中 RAB10水平差异无统计学意义(F=2.309，P=0.121)。结论 HIE患儿miR-374a-5p呈低表达，且与病情严重程度有关，即病情越严重miR-374a-5p表达水平越低，可作为HIE早期诊断和病情评估的参考依据。
- 缺氧缺血性脑病 /
- 微小RNA-374a-5p /
- 早期诊断 /
- 病情评估 /
- 新生儿
Abstract: Objective To investigate the expression levels and clinical significance of microRNA-374a-5p (miR-374a-5p) and RAB10 proteins in cord blood of neonates with hypoxic-ischemic encephalopathy (HIE). Methods A total of 75 newborns born in the First Affiliated Hospital of Bengbu Medical College from December 2020 to August 2022 were selected and divided into perinatal asphyxia group (26 cases) and HIE group (27 cases) according to the inclusion and exclusion criteria of HIE and whether the children had asphyxia. There were 14 cases in the mild HIE group, 7 cases in the moderate HIE group, 6 cases in the severe HIE group, and 22 cases in the healthy group. Umbilical cord blood was collected within 30 min after birth, and the expression levels of miR-374a-5p and RAB10 proteins were detected by real-time fluorescence quantification (qRT-PCR). Results There were no significant differences in gender, delivery mode, gestational age and birth weight among all groups (P>0.05). There were significant differences in miR-374a-5p (F=340.618, P < 0.001) and RAB10 (F=100.906, P < 0.001) among the asphyxia group, HIE group and healthy group. The expression level of serum miR-374a-5p in cord blood of neonates in HIE group was lower than that in healthy group, and RAB10 were higher than that in healthy group, the differences were statistically significant (all P < 0.05). The comparison of miR-374a-5p among the three groups with mild, moderate and severe HIE showed statistically significant differences (0.11±0.03, 0.08±0.03, 0.03±0.01, F=39.403, P < 0.001), the expression level of miR-374a-5p in moderate group was lower than that in mild group, and that in severe group was lower than that in mild group and moderate group, the differences were statistically significant (all P < 0.05). There was no significant difference in RAB10 level in cord blood among the three groups with mild, moderate and severe HIE (F=2.309, P=0.121). Conclusion The expression of miR-374a-5p expression is low in HIE children, which is related to the severity of the disease, the more severe the disease, the lower the expression level of miR-374a-5p, which can be used as a reference for early diagnosis and disease evaluation of HIE.
- Hypoxic-ischemic encephalopathy /
- MicroRNA-374a-5p /
- Early diagnosis /
- Assessment of illness /
- Newborn

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表 1 miR-374a-5p、RAB10以及内参U6的引物序列

Table 1. Primer sequences for miR-374a-5p, RAB10, and the reference gene U6

项目	正向引物5’~3’	反向引物5’~3’
miR-374a-5p	CGCGCGTTATAATACAACCTGA	AGTGCAGGGTCCGAGGTATT
RAB10	CAAGGGAGCATGGTATTAGGTTT	CTAACGTGAGGAACGCCTTTT
U6	AGAGAAGATTAGCATGGCCCCTG	ATCCAGTGCAGGGTCCGAGG

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表 2 各组新生儿基本资料比较

Table 2. Comparison of basic information among different groups of newborns

组别	例数	性别(例)		胎龄(x±s, 周)	分娩方式(例)		出生体重(x±s, g)
组别	例数	男	女	胎龄(x±s, 周)	顺产	剖宫产	出生体重(x±s, g)
健康组	22	17	5	37.77±1.90	9	13	3 228±486
窒息组	26	18	8	35.31±3.45	11	15	2 783±863
HIE轻度组	14	8	6	36.50±2.34	7	7	2 850±746
HIE中度组	7	4	3	36.71±1.38	3	4	2 987±378
HIE重度组	6	4	2	36.33±4.13	2	4	2 898±961
统计量		2.030^a		2.359^b	0.551^a		1.251^b
P值		0.730		0.062	0.968		0.298
注：^a为χ²值，^b为F值。

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表 3 各组新生儿脐带血中miR-374a-5p、RAB10比较(x±s)

Table 3. Comparison of miR-374a-5p and RAB10 in neonatal cord blood of each group (x±s)

组别	例数	miR-374a-5p	RAB10
HIE组	27	0.09±0.04	2.68±0.44
健康组	22	0.83±0.11^a	1.01±0.15^a
窒息组	26	0.33±0.13^ab	2.57±0.60^b
F值		340.618	100.906
P值		< 0.001	< 0.001
注：与HIE组比较，^aP < 0.01；与健康组比较，^bP < 0.01。

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表 4 不同严重程度HIE组新生儿脐带血中miR-374a-5p、RAB10比较(x±s)

Table 4. Comparison of miR-374a-5p and RAB10 levels in neonatal cord blood in different severity groups of HIE (x±s)

组别	例数	miR-374a-5p	RAB10
轻度组	14	0.11±0.03	2.57±0.47
中度组	7	0.08±0.03^a	2.97±0.25
重度组	6	0.03±0.01^ab	2.55±0.44
F值		39.403	2.309
P值		< 0.001	0.121
注：与轻度组比较，^aP < 0.01；与中度组比较，^bP < 0.01。

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参考文献(20)

[1]	YANG W L, WANG L L, TIAN T, et al. Maternal hypertensive disorders in pregnancy and risk of hypoxic-ischemia encephalopathy[J]. J Matern Fetal Neonatal Med, 2021, 34(11): 1754-1762. doi: 10.1080/14767058.2019.1647529
[2]	何东梅, 黄杜仙, 肖坤茂, 等. 缺氧缺血性脑病新生儿预后不良的危险因素分析及护理对策[J]. 全科护理, 2021, 19(11): 1508-1511. doi: 10.12104/j.issn.1674-4748.2021.11.019 HE D M, HUANG D X, XIAO K M, et al. Risk factors and nursing strategies of poor prognosis in neonates with hypoxic-ischemic encephalopathy[J]. Chinese General Practice Nursing, 2021, 19(11): 1508-1511. doi: 10.12104/j.issn.1674-4748.2021.11.019
[3]	阎炯, 胡玉莲, 王维鹏. 脐带血检测在新生儿缺血缺氧性脑病诊断中的价值[J]. 中国临床医生杂志, 2020, 48(11): 1360-1363. doi: 10.3969/j.issn.2095-8552.2020.11.031 YAN J, HU Y L, WANG W P. The value of umbilical cord blood detection in the diagnosis of neonatal hypoxic ischemic encephalopathy[J]. Chinese Journal For Clinicians, 2020, 48(11): 1360-1363. doi: 10.3969/j.issn.2095-8552.2020.11.031
[4]	O' SULLIVAN M P, LOONEY A M, MOLONEY G M, et al. Validation of altered umbilical cord blood microRNA expression in neonatal hypoxic-ischemic encephalopathy[J]. JAMA Neurol, 2019, 76(3): 333-341. doi: 10.1001/jamaneurol.2018.4182
[5]	JIANG F, YANG M, WU C Y, et al. Potential roles of miR-374a-5p in mediating neuroprotective effects and related molecular mechanism[J]. J Mol Neurosci, 2019, 69(1): 123-132. doi: 10.1007/s12031-019-01340-w
[6]	CHEN Z, HU Y, LU R F, et al. microRNA-374a-5p inhibits neuroinflammation in neonatal hypoxic-ischemic encephalopathy via regulating NLRP3 inflammasome targeted Smad6[J]. Life Sci, 2020, 252: 117664. DOI: 10.1016/j.lfs.2020.117664.
[7]	ZHANG Y J, PAN Q, YU Y, et al. microRNA-519d induces autophagy and apoptosis of human hepatocellular carcinoma cells through activation of the AMPK signaling pathway via Rab10[J]. Cancer Manag Res, 2020, 12: 2589-2602. doi: 10.2147/CMAR.S207548
[8]	中华医学会儿科学分会新生儿学组. 新生儿缺氧缺血性脑病诊断标准[J]. 中国当代儿科杂志, 2005, 7(2): 97-98. https://www.cnki.com.cn/Article/CJFDTOTAL-DDKZ200502000.htm Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association. Diagnostic criteria for neonatal hypoxic-ischemic encephalopathy[J]. The Chinese Journal of Contemporary Pediatrics, 2005, 7(2): 97-98. https://www.cnki.com.cn/Article/CJFDTOTAL-DDKZ200502000.htm
[9]	陈小娜, 姜毅. 2018昆士兰临床指南: 缺氧缺血性脑病介绍[J]. 中华新生儿科杂志, 2019, 34(1): 77-78. https://www.cnki.com.cn/Article/CJFDTOTAL-XIBU202209002.htm CHEN X N, JIANG Y. 2018 Queensland Clinical guideline: Introduction to hypoxic-ischemic encephalopathy[J]. Chinese Journal of Neonatology, 2019, 34(1): 77-78. https://www.cnki.com.cn/Article/CJFDTOTAL-XIBU202209002.htm
[10]	孔雯, 蒋玮玮, 孔德川, 等. 新生儿缺血缺氧性脑病发生情况及影响因素[J]. 中国妇幼保健, 2019, 34(17): 3963-3965. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFYB201917030.htm KONG W, JIANG W W, KONG D C, et al. The incidence and influencing factors of hypoxic ischemic encephalopathy in neonates[J]. Maternal and Child Health Care of China, 2019, 34(17): 3963-3965. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFYB201917030.htm
[11]	PEEPLES E S, SAHAR N E, SNYDER W, et al. Temporal brain microRNA expression changes in a mouse model of neonatal hypoxic-ischemic injury[J]. Pediatr Res, 2022, 91(1): 92-100. doi: 10.1038/s41390-021-01701-5
[12]	刘婧, 张云虹, 赵霖, 等. 深静脉血栓形成患者外周血miR-374a-5p、IL-10水平变化及其调控关系[J]. 山东医药, 2019, 59(5): 13-16. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYY201905005.htm LIU J, ZHANG Y H, ZHAO L, et al. Changes in levels of miR-374a-5p and IL-10 in peripheral blood of DVT patients and the relationship between them[J]. Shandong Medical Journal, 2019, 59(5): 13-16. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYY201905005.htm
[13]	李博文, 李世清, 周君. 血清miR-374a-5p、miR-205水平对髋膝关节置换后下肢深静脉血栓形成诊断的价值[J]. 医药论坛杂志, 2021, 42(10): 81-85. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX202110023.htm LI B W, LI S Q, ZHOU J. The value of serum miR-374a-5p and miR-205 in the diagnosis of lower extremity deep vein thrombosis after hip and knee arthroplasty[J]. Journal of Medical Forum, 2021, 42(10): 81-85. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX202110023.htm
[14]	金浩, 余佳, 王梓瑜, 等. DLEU2下调miR-374a-5p对肝癌细胞增殖、凋亡、迁移、侵袭的影响[J]. 中国老年学杂志, 2021, 41(17): 3770-3776. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLXZ202117042.htm JIN H, YU J, WANG Z Y, et al. Effect of DLEU2 down-regulation of miR-374a-5p on proliferation, apoptosis, migration and invasion of hepatocellular carcinoma cells[J]. Chinese Journal of Gerontology, 2021, 41(17): 3770-3776. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLXZ202117042.htm
[15]	贾冬冬, 黄江浩, 汪奇云, 等. 血浆miR-374a-5p作为肺癌诊治指标的临床价值研究[J]. 黑龙江中医药, 2021, 50(5): 28-29. https://www.cnki.com.cn/Article/CJFDTOTAL-HLZY202105022.htm JIA D D, HUANG J H, WANG Q Y, et al. Clinical value of plasma miR-374a-5p as the index of diagnosis and treatment of lung cancer[J]. Heilongjiang Journal of Traditional Chinese Medicine, 2021, 50(5): 28-29. https://www.cnki.com.cn/Article/CJFDTOTAL-HLZY202105022.htm
[16]	卓飞翔, 张阵, 陈信. MiRNA对新生儿缺氧缺血性脑病脑保护作用的研究进展[J]. 生命的化学, 2022, 42(9): 1746-1751. https://www.cnki.com.cn/Article/CJFDTOTAL-SMHX202209017.htm ZHUO F X, ZHANG Z, CHEN X. Research progress on the cerebral protective effect of miRNA on neonatal hypoxic-ischemic encephalopathy[J]. Chemistry of Life, 2022, 42(9): 1746-1751. https://www.cnki.com.cn/Article/CJFDTOTAL-SMHX202209017.htm
[17]	CHUA C E L, TANG B L. Rab 10-a traffic controller in multiple cellular pathways and locations[J]. J Cell Physiol, 2018, 233(9): 6483-6494.
[18]	DENG C Y, LEI W L, XU X H, et al. JIP1 mediates anterograde transport of RAB10 cargos during neuronal polarization[J]. J Neurosci, 2014, 34(5): 1710-1723.
[19]	WAUTERS F, CORNELISSEN T, IMBERECHTS D, et al. LRRK2 mutations impair depolarization-induced mitophagy through inhibition of mitochondrial accumulation of RAB10 [J]. Autophagy, 2020, 16(2): 203-222.
[20]	周家兴, 吴乃胜. 新生儿缺氧缺血性脑病血清IL-34水平及其与Th17相关细胞因子和NABA评分的相关性[J]. 中华全科医学, 2020, 18(9): 1527-1529. doi: 10.16766/j.cnki.issn.1674-4152.001551 ZHOU J X, WU N S. Serum IL-34 level in neonates with hypoxic-ischemic encephalopathy and its correlation with Th17-related cytokines and NABA scores[J]. Chinese Journal of General Practice, 2020, 18(9): 1527-1529. doi: 10.16766/j.cnki.issn.1674-4152.001551