[1]叶莉娜,张 乐.干扰素调控因子4对缺氧缺血性脑病新生大鼠炎症反应及血脑屏障功能的影响[J].陕西医学杂志,2020,49(11):1375-1378.[doi:DOI:10.3969/j.issn.1000-7377.2020.11.002]
 YE Lina,ZHANG Le..Effect of IRF4 on inflammatory response and blood-brain barrier function in neonatal rats with hypoxic ischemic encephalopathy[J].,2020,49(11):1375-1378.[doi:DOI:10.3969/j.issn.1000-7377.2020.11.002]
点击复制

干扰素调控因子4对缺氧缺血性脑病新生大鼠炎症反应及血脑屏障功能的影响
分享到:

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
49
期数:
2020年11期
页码:
1375-1378
栏目:
基础研究
出版日期:
2020-11-05

文章信息/Info

Title:
Effect of IRF4 on inflammatory response and blood-brain barrier function in neonatal rats with hypoxic ischemic encephalopathy
作者:
叶莉娜1张 乐2
1.陕西省渭南市妇幼保健院(渭南 714000); 2.内蒙古自治区乌兰察布市凉城县医院(乌兰察布 013750)
Author(s):
YE LinaZHANG Le.
Weinan Maternal and Child Health Hospital,Shaanxi Province(Weinan 714000)
关键词:
干扰素调控因子4 新生大鼠 缺氧缺血性脑病 炎症 血脑屏障
Keywords:
Interferon regulatory factor 4 Neonatal rats Hypoxic-ischemic encephalopathy Inflammation Blood-brain barrier
分类号:
R722.19
DOI:
DOI:10.3969/j.issn.1000-7377.2020.11.002
文献标志码:
A
摘要:
目的:采用新生大鼠缺氧缺血性脑病(HIE)模型,研究干扰素调控因子4(IRF4)对HIE新生大鼠炎症反应和血脑屏障功能的影响,为临床应用IRF4治疗新生儿缺氧缺血性脑病提供实验依据。方法:选取10日龄健康雄性SD大鼠10只作为对照组,10只IRF4基因敲除SD大鼠用RVM法制作HIE模型作为IRF4KO组。HIE后7 d测定脑萎缩和行为缺陷,ELISA法测定血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)和白细胞介素-4(IL-4)水平,ELISA检测血清中基质金属蛋白酶-9(MMP-9)水平,免疫组织化学检测脑组织中MMP-9水平。结果:HIE后7 d,IRF4KO组新生大鼠较对照组脑萎缩严重,表现行为缺陷,且血清中促炎因子TNF-α、IL-1β水平增加,抑炎因子IL-10、IL-4水平下降,MMP-9水平显著升高,表明炎症反应增加,血脑屏障功能显著受损。结论:IRF4在新生大鼠HIE的神经炎症及血脑屏障功能中起调节作用,提示IRF4可能是新生儿缺血性脑损伤的潜在治疗靶点。
Abstract:
Objective:To study the effect of interferon regulatory factor 4(IRF4)on the inflammatory response and blood-brain barrier function of hypoxic-ischemic encephalopathy(HIE)neonatal rats by adopting a HIE model in neonatal rats,and to provide experimental evidence for clinical application of IRF4.Methods:Ten 10-day-old healthy male SD rats were selected as the control group,and 10 IRF4 gene knockout SD rats were used to make HIE models by RVM as the IRF4KO group.Brain atrophy and behavioral deficits were measured 7 days after HIE.Serum levels of cytokines such as TNF-α,IL-1β,IL-10,IL-4 and MMP-9 were determined by ELISA.MMP-9 levels in brain tissue was detected by immunohistochemical method.Results:7 days after HIE,neonatal rats in the IRF4KO group had more severe brain atrophy than the control group,exhibited behavioral defects,and serum pro-inflammatory factors TNF-α and IL-1β levels increased,and anti-inflammatory factors IL-10 and IL-4 levels decreased,and MMP-9 level significantly increased,which indicated that the inflammatory response increased and the BBB function was significantly impaired.Conclusion:IRF4 plays a regulatory role in neuroinflammation and BBB function,suggesting that IRF4 can serve as a potential therapeutic target for neonatal ischemic brain injury.

参考文献/References:

[1] 陈 巍,唐 静.新生儿中重度缺氧缺血性脑病中运用头部亚低温治疗的时间与疗效相关性分析[J].陕西医学杂志,2019,48(3):338-340,344.
[2] 李小晶,朱海霞,甘颖妍,等.神经节苷脂治疗新生儿缺氧缺血性脑病对血气及血清炎症因子水平的影响[J].海南医学院学报,2017,23(4):549-552.
[3] 鲁 旭,姜 泓,张渊韬.新生儿缺氧缺血性脑病发病机制研究进展[J].新乡医学院学报,2016,33(10):929-927.
[4] 张 珺,杨 菁.干扰素调节因子4与T细胞分化及免疫性疾病的研究进展[J].医学综述,2016,22(1):9-12.
[5] Chistiakov DA,Myasoedova VA,Revin VV,et al.The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2 [J].Immunobiology,2018,223(1):101-111.
[6] Zhao SC,Wang C,Xu H,et al.Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice [J].Acta Pharmacol Sin,2017,38(11):1425-1434.
[7] Honma K,Udono H,Kohno T,et al.Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS [J].Proc Natl Acad Sci USA,2005,102(44):16001-16006.
[8] Demarest TG,Waite EL,Kristian T,et al.Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia ischemia[J].Neuroscience,2016,335:103-113.
[9] Almamun A,Chauhan A,Yu H,et al.Interferon regulatory factor 4/5 signaling impacts on microglial activation after ischemic stroke in mice[J].Eur J Neurosci,2018,47(2):140-149.
[10] 孔艳英,刘丽伟,李 馨.不同神经发育学评估方法在新生儿缺氧缺血性脑病随访或后遗症中的应用[J].中国妇幼保健,2015,30(32):5590-5592.
[11] Satoh T,Takeuchi O,Vandenbon A,et al.The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection[J].Nat Immunol,2010,11(10):936-944.
[12] Guo S,Li ZZ,Jiang DS,et al.IRF4 is a novel mediator for neuronal survival in ischaemic stroke[J].Cell Death Differ,2014,21(6):888-903.
[13] Ahyi AN,Chang HC,Dent AL,et al.IFN regulatory factor 4 regulates the expression of a subset of Th2 cytokines[J].J Immunol,2009,183(3):1598-1606.
[14] Jickling GC,Liu D,Ander BP,et al.Targeting neutrophils in ischemic stroke:translational insights from experimental studies[J].J Cerebr Blood Flow Metabol,2015,35(6):888-901.
[15] Almamun A,Yu H,Romana S,et al.Inflammatory responses are sex specific in chronic hypoxic-ischemic encephalopathy[J].Cell Transplant,2018,27(9):1328-1339.
[16] Turner RJ,Sharp FR.Implications of MMP9 for blood brain barrier disruption and hemorrhagic transformation following ischemic stroke[J].Front Cell Neurosci,2016,43:1056.
[17] 王艳民.开窍活血汤对脑梗死患者血清前白蛋白、MCP-1及MMP-9的影响[J].陕西中医,2019,40(1):34-36.

更新日期/Last Update: 2020-11-05