新生儿缺氧缺血性脑病的病因和发病机制研究进展
摘要
新生儿缺氧缺血性脑病(HIE)是由于围生期多种因素导致的脑血流减少的一种缺氧缺血性损伤,并在临床上出现一系列脑功能受损的表现。HIE病情重,病死率高。近年来,随着围生期医学诊疗技术水平的提高,HIE患儿的存活率也逐年上升,但与此同时,幸存的部分患儿可留有不同程度的神经系统后遗症,给家庭及社会的长期发展带来严重后果,因此,阐明导致新生儿HIE的各种病因及其发病机制至关重要,有利于从HIE发生的源头给予积极防治,有效降低HIE的发病率和伤残率,减少远期后遗症的发生。本文主要对早产和缺氧、宫内感染及高温导致HIE的发生机制进行综述。
引文
[1]王静,陈晨,郑茂.新生儿缺氧缺血性脑病后遗症发生情况及其影响因素分析[J].海南医学,2014,25(8):1199-1200.
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[4] FRIBERG H,CRONBERG T. Hypoxic-ischemic encephalopathy[J].Semin Neurol,2017,37(1):3-4.
[5] XIE B,GU P,WANG W,et al. Therapeutic effects of human umbilical cord mesenchymal stem cells transplantation on hypoxic ischemic encephalopathy[J]. Am J Transl Res,2016,8(7):3241-3250.
[6] ZHAO M,ZHU P,FUJINO M,et al. Oxidative stress in hypoxicischemic encephalopathy:molecular mechanisms and therapeutic strategies[J]. Int J Mol Sci,2016,17(12):E2078.
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[8]江佩芳,朱涛,杨翠微,等.宫内感染致脑损伤对仔鼠认知发育和海马神经发生的影响[J].中国病理生理杂志,2014,30(11):1934-1940.
[9]朱莹雯,丁晓春.组织激肽释放酶8在宫内感染脑白质损伤仔鼠海马及血清中的表达[J].中国新生儿科杂志,2017,32(5):379-383.
[10]韩彤妍,杨孜,朴梅花.绒毛膜羊膜炎与胎儿及新生儿疾病[J].中国实用妇科与产科杂志,2016,32(6):529-534.
[11] MISHIMA K,IKEDA T,YOSHIKAWA T,et al. Selective and long-term learning impairment following neonatal hypoxicischemic brain insult in rats[J]. Behav Brain Res,2001,118(1):17-25.
[12] MURRAY D M,O'CONNOR C M,RYAN C A,et al. Early EEG grade and outcome at 5 years after mild neonatal hypoxic ischemic encephalopathy[J]. Pediatrics,2016,138(4):e20160659.
[13] DEL R R,OCHOA C,ALARCON A,et al. Amplitude integrated electroencephalogram as a prognostic tool in neonates with hypoxic-ischemic encephalopathy:a systematic review[J]. PLoS One,2016,11(11):e0165744.
[14] REINBOTH B S,KOSTER C,ABBERGER H,et al. Endogenous hypothermic response to hypoxia reduces brain injury:implications for modeling hypoxic-ischemic encephalopathy and therapeutic hypothermia in neonatal mice[J]. Exp Neurol,2016,283(Pt A):264-275.
[15] HUA C,JU W N,JIN H,et al. Molecular chaperones and hypoxicischemic encephalopathy[J]. Neural Regen Res,2017,12(1):153-160.
[16] NATARAJAN G,PAPPAS A,SHANKARAN S. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxicischemic encephalopathy(HIE)[J]. Semin Perinatol,2016,40(8):549-555.
[17] YANG L,LI D,CHEN S. Hydrogen water reduces NSE,IL-6,and TNF-αlevels in hypoxic-ischemic encephalopathy[J]. Open Med,2016,11(1):399-406.
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[19] MUNIRAMAN H,GARDNER D,SKINNER J,et al. Erratum to:biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia[J].Eur J Pediatr,2017,176(10):1305-1306.
[20] KASDORF E,PERLMAN J M. Hyperthermia,inflammation,and perinatal brain injury[J]. Pediatr Neurol,2013,49(1):8-14.
[21]许丽萍,任榕娜.绒毛膜羊膜炎与早产儿脑损伤的研究进展[J].医学综述,2015,21(6):967-969.
[22]吴卫卫,吴寒冰,朱小玉,等.阴道试产中转剖宫产术后产褥期感染的影响因素和病原微生物耐药性分析[J].中国妇幼保健,2017,32(5):898-900.
[23] CUI D,SUN D,WANG X,et al. Impaired autophagosome clearance contributes to neuronal death in a piglet model of neonatal hypoxic-ischemic encephalopathy J]. Cell Death Dis,2017,8(7):e2919.
[24] LEMMON M E,WAGNER M W,BOSEMANI T,et al. Diffusion tensor imaging detects occult cerebellar injury in severe neonatal hypoxic-ischemic encephalopathy[J]. Dev Neurosci,2017,39(1/2/3/4):207-214.
[25] LI H X,FENG X,WANG Q,et al. Diffusion tensor imaging assesses white matter injury in neonates with hypoxic-ischemic encephalopathy[J]. Neural Regen Res,2017,12(4):603-609.
[26] YANG C S,LIN Y Z,GUO Q,et al. Chinese herbal medicine Xingnaojing injection for hypoxic ischemic encephalopathy in newborns:a systematic review and meta-analysis[J]. Chin J Integr Med,2018,24(2):147-155.
[27] FAINGOLD R,CASSIA G,PREMPUNPONG C,et al. Intestinal ultrasonography in infants with moderate or severe hypoxicischemic encephalopathy receiving hypothermia[J]. Pediatr Radiol,2016,46(1):87-95.
[28] LOWE D W,HOLLIS B W,WAGNER C L,et al. Vitamin D insufficiency in neonatal hypoxic-ischemic encephalopathy[J].Pediatr Res,2017,82(1):55-62.
[29] AMARNATH C,HELEN M T,PERIAKARUPAN A,et al. Neonatal parechovirus leucoencephalitis-radiological pattern mimicking hypoxic-ischemic encephalopathy[J]. Eur J Radiol,2016,85(2):428-434.
[30] ADHIKARI S,RAO K S. Neurodevelopmental outcome of term infants with perinatal asphyxia with hypoxic ischemic encephalopathy stage II[J]. Brain Dev,2016,39(2):107-111.
[31]杨祖钦,余坚,何笑笑,等. sTREM-1与PCT对围生期宫内感染合并肺炎新生儿肺出血的影响研究[J].中华医院感染学杂志,2016,26(16):3816-3818.
[32] RASMUSSEN L A,BELL E,RACINE E. A qualitative study of physician perspectives on prognostication in neonatal hypoxic ischemic encephalopathy[J]. J Child Neurol,2016,31(11):1312-1319.
[33]杨晓宇,李向红,雷丽莉,等.早产儿脑白质损伤临床高危因素分析[J].中国综合临床,2016,32(8):739-743.
[34]李佳帅,朱路文,叶涛,等.外泌体在缺血性脑卒中的研究进展[J].中国康复理论与实践,2018,24(6):654-658.
[35]邓诗桦,金圣娟,付溪,等.活化蛋白C在脂多糖诱导小胶质细胞活化中的作用[J].中华围产医学杂志,2016,19(4):294-300.
[36]王智英,霍海花,吕红艳,等.脐血NF-kB及MBP检测对早产儿脑白质损伤的早期诊断及其与预后的关系[J].川北医学院学报,2017,32(4):518-521.
[37]江佩芳. CREB信号通路调控宫内炎症后仔鼠海马神经发生及分子机制研究[D].杭州:浙江大学,2012.
[38]孙涛.急性脑梗死患者血清MMP-9和D-二聚体水平及与传统危险因素的相关性分析[D].济南:山东大学,2014.
[39] LEE B S,JUNG E,LEE Y,et al. Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy[J]. Cell Stress Chaperones,2017,22(3):409-415.
[40]车浩,阮语嫣,骆汤艳,等.炎症反应中Toll样受体对NHE蛋白家族的调节[J].生理学报,2018,70(5):521-530.
[2]王来栓,邹亮燕.间充质干细胞移植治疗新生儿缺氧缺血性脑病研究进展[J].中华实用儿科临床杂志,2018,33(2):81-85.
[3] BARKHUIZEN M,VAN DEN HOVE D L,VLES J S,et al. 25years of research on global asphyxia in the immature rat brain[J].Neurosci Biobehav Rev,2017,75(29):166-182.
[4] FRIBERG H,CRONBERG T. Hypoxic-ischemic encephalopathy[J].Semin Neurol,2017,37(1):3-4.
[5] XIE B,GU P,WANG W,et al. Therapeutic effects of human umbilical cord mesenchymal stem cells transplantation on hypoxic ischemic encephalopathy[J]. Am J Transl Res,2016,8(7):3241-3250.
[6] ZHAO M,ZHU P,FUJINO M,et al. Oxidative stress in hypoxicischemic encephalopathy:molecular mechanisms and therapeutic strategies[J]. Int J Mol Sci,2016,17(12):E2078.
[7] MASSARO A N,MURTHY K,ZANILETTI I,et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy:a report from the children's hospitals neonatal consortium HIE focus group[J]. J Perinatol,2016,35(4):290-296.
[8]江佩芳,朱涛,杨翠微,等.宫内感染致脑损伤对仔鼠认知发育和海马神经发生的影响[J].中国病理生理杂志,2014,30(11):1934-1940.
[9]朱莹雯,丁晓春.组织激肽释放酶8在宫内感染脑白质损伤仔鼠海马及血清中的表达[J].中国新生儿科杂志,2017,32(5):379-383.
[10]韩彤妍,杨孜,朴梅花.绒毛膜羊膜炎与胎儿及新生儿疾病[J].中国实用妇科与产科杂志,2016,32(6):529-534.
[11] MISHIMA K,IKEDA T,YOSHIKAWA T,et al. Selective and long-term learning impairment following neonatal hypoxicischemic brain insult in rats[J]. Behav Brain Res,2001,118(1):17-25.
[12] MURRAY D M,O'CONNOR C M,RYAN C A,et al. Early EEG grade and outcome at 5 years after mild neonatal hypoxic ischemic encephalopathy[J]. Pediatrics,2016,138(4):e20160659.
[13] DEL R R,OCHOA C,ALARCON A,et al. Amplitude integrated electroencephalogram as a prognostic tool in neonates with hypoxic-ischemic encephalopathy:a systematic review[J]. PLoS One,2016,11(11):e0165744.
[14] REINBOTH B S,KOSTER C,ABBERGER H,et al. Endogenous hypothermic response to hypoxia reduces brain injury:implications for modeling hypoxic-ischemic encephalopathy and therapeutic hypothermia in neonatal mice[J]. Exp Neurol,2016,283(Pt A):264-275.
[15] HUA C,JU W N,JIN H,et al. Molecular chaperones and hypoxicischemic encephalopathy[J]. Neural Regen Res,2017,12(1):153-160.
[16] NATARAJAN G,PAPPAS A,SHANKARAN S. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxicischemic encephalopathy(HIE)[J]. Semin Perinatol,2016,40(8):549-555.
[17] YANG L,LI D,CHEN S. Hydrogen water reduces NSE,IL-6,and TNF-αlevels in hypoxic-ischemic encephalopathy[J]. Open Med,2016,11(1):399-406.
[18] KRISHNAN P,SHROFF M. Neuroimaging in neonatal hypoxic ischemic encephalopathy[J]. Indian J Pediatr,2016,83(9):995-1002.
[19] MUNIRAMAN H,GARDNER D,SKINNER J,et al. Erratum to:biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia[J].Eur J Pediatr,2017,176(10):1305-1306.
[20] KASDORF E,PERLMAN J M. Hyperthermia,inflammation,and perinatal brain injury[J]. Pediatr Neurol,2013,49(1):8-14.
[21]许丽萍,任榕娜.绒毛膜羊膜炎与早产儿脑损伤的研究进展[J].医学综述,2015,21(6):967-969.
[22]吴卫卫,吴寒冰,朱小玉,等.阴道试产中转剖宫产术后产褥期感染的影响因素和病原微生物耐药性分析[J].中国妇幼保健,2017,32(5):898-900.
[23] CUI D,SUN D,WANG X,et al. Impaired autophagosome clearance contributes to neuronal death in a piglet model of neonatal hypoxic-ischemic encephalopathy J]. Cell Death Dis,2017,8(7):e2919.
[24] LEMMON M E,WAGNER M W,BOSEMANI T,et al. Diffusion tensor imaging detects occult cerebellar injury in severe neonatal hypoxic-ischemic encephalopathy[J]. Dev Neurosci,2017,39(1/2/3/4):207-214.
[25] LI H X,FENG X,WANG Q,et al. Diffusion tensor imaging assesses white matter injury in neonates with hypoxic-ischemic encephalopathy[J]. Neural Regen Res,2017,12(4):603-609.
[26] YANG C S,LIN Y Z,GUO Q,et al. Chinese herbal medicine Xingnaojing injection for hypoxic ischemic encephalopathy in newborns:a systematic review and meta-analysis[J]. Chin J Integr Med,2018,24(2):147-155.
[27] FAINGOLD R,CASSIA G,PREMPUNPONG C,et al. Intestinal ultrasonography in infants with moderate or severe hypoxicischemic encephalopathy receiving hypothermia[J]. Pediatr Radiol,2016,46(1):87-95.
[28] LOWE D W,HOLLIS B W,WAGNER C L,et al. Vitamin D insufficiency in neonatal hypoxic-ischemic encephalopathy[J].Pediatr Res,2017,82(1):55-62.
[29] AMARNATH C,HELEN M T,PERIAKARUPAN A,et al. Neonatal parechovirus leucoencephalitis-radiological pattern mimicking hypoxic-ischemic encephalopathy[J]. Eur J Radiol,2016,85(2):428-434.
[30] ADHIKARI S,RAO K S. Neurodevelopmental outcome of term infants with perinatal asphyxia with hypoxic ischemic encephalopathy stage II[J]. Brain Dev,2016,39(2):107-111.
[31]杨祖钦,余坚,何笑笑,等. sTREM-1与PCT对围生期宫内感染合并肺炎新生儿肺出血的影响研究[J].中华医院感染学杂志,2016,26(16):3816-3818.
[32] RASMUSSEN L A,BELL E,RACINE E. A qualitative study of physician perspectives on prognostication in neonatal hypoxic ischemic encephalopathy[J]. J Child Neurol,2016,31(11):1312-1319.
[33]杨晓宇,李向红,雷丽莉,等.早产儿脑白质损伤临床高危因素分析[J].中国综合临床,2016,32(8):739-743.
[34]李佳帅,朱路文,叶涛,等.外泌体在缺血性脑卒中的研究进展[J].中国康复理论与实践,2018,24(6):654-658.
[35]邓诗桦,金圣娟,付溪,等.活化蛋白C在脂多糖诱导小胶质细胞活化中的作用[J].中华围产医学杂志,2016,19(4):294-300.
[36]王智英,霍海花,吕红艳,等.脐血NF-kB及MBP检测对早产儿脑白质损伤的早期诊断及其与预后的关系[J].川北医学院学报,2017,32(4):518-521.
[37]江佩芳. CREB信号通路调控宫内炎症后仔鼠海马神经发生及分子机制研究[D].杭州:浙江大学,2012.
[38]孙涛.急性脑梗死患者血清MMP-9和D-二聚体水平及与传统危险因素的相关性分析[D].济南:山东大学,2014.
[39] LEE B S,JUNG E,LEE Y,et al. Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy[J]. Cell Stress Chaperones,2017,22(3):409-415.
[40]车浩,阮语嫣,骆汤艳,等.炎症反应中Toll样受体对NHE蛋白家族的调节[J].生理学报,2018,70(5):521-530.