Research progress on hyperoxia-induced brain injury in preterm infants
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摘要:
新生儿重症监护室(NICU)技术的发展，使得氧疗普遍应用于早产儿抢救治疗中，提高了早产儿存活率。然而，与高氧相关的早产儿脑病(EOP)、早产儿视网膜病(ROP)和支气管肺发育不良(BPD)等并发症严重影响存活早产儿的生存质量。本文综述了高氧导致脑损伤的临床及动物实验研究现状，明确与高氧相关早产儿神经系统损伤可能的表现及机制，为早产儿临床安全用氧决策提供理论依据。
Abstract:With the advances of technology in neonatal intensive care unit (NICU), oxygen therapy in the resuscitation and treatment of preterm infants is widely applied, which significantly improves their survival rates.However, complications associated with hyperoxia, such as early onset preterm encephalopathy (EOP), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), severely affect the quality of life of surviving preterm infants.This article reviewed the current clinical and animal experimental research on hyperoxia-induced brain injury, clarifying the potential manifestations and mechanisms of neurological damage related to hyperoxia in preterm infants.The findings provide a theoretical basis for safe oxygen use decisions in clinical practice for preterm infants.
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Keywords:
- hyperoxia /
- brain injury /
- bronchopulmonary dysplasia /
- preterm infant /
- animal experiments /
- neonate
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表 1 高氧导致脑损伤动物模型及验证
动物 FiO2 高氧暴露开始时间 高氧暴露持续时间 脑损伤区域 损伤细胞及变化趋势 Wistar rat[14] 80% P6 24 h 脑白质、灰质丘脑、海马 OLs凋亡增加 Wistar rat[15] 80% P6 24 h 小脑 AS产生生长因子减少; OPCs增殖减少及成熟障碍; OLs凋亡增加 Wistar rat[16] 80% P6 24 h 小脑皮质 Neu: GCPs增殖及成熟减少、凋亡增加; PC树突形成延迟、分支减少 Wistar rat[17] 80% P6 24 h 脑白质: 外囊、胼胝体 OPCs增殖减少、成熟障碍、凋亡增加、髓鞘形成不足; MG活化 Wistar ratsynRas-transgenic mice[18] 80% P7 24 h 尾状核、伏隔核、额叶、顶叶、扣带、压后皮质、前脑内的白质束 Neu凋亡 Sprague-Dawley rat[19] 80% P6 24 h — Neu谷氨酸分泌增加，兴奋性毒性损伤 C57BL/6 WT mice[20] 80% P5 48 h 脑灰质 GABA能中间神经元功能损伤及成熟障碍 C57BL/6 WT mice[3] 80% P5 48 h 脑灰质 OLs神经营养因子表达减少、髓鞘形成减少; GABA能中间神经元成熟障碍及细胞损伤 Sprague-Dawley rat[21] 80% P6 48 h — — Wistar rat[22] 80% P3 48 h 脑白质 OPCs髓鞘形成不足 C57BL/6 WT mice[8] 80% P4 4 d 外囊、脑室下区、脑室周围区 外囊: OLs减少、毛细血管减少; 脑白质: AS增生; 脑室下区: 细胞凋亡增加; 脑室周围区: 毛细血管减少 Sprague-Dawley rat[23] 80% P1 6 d 脑灰质、海马 — — 80% P6 24 h — Neu兴奋性毒性损伤: 谷氨酸转运体表达下降，谷氨酸在突触间隙堆积[24] C57BL/6 WT mice[25] 80%~85% P6 48 h 海马 NPCs生成减少、凋亡增加; 中间神经元减少、树突分支减少 Wistar rat[26] 85% P1/P3/P7 24 h/72 h/7 d 脑灰质 Neu凋亡增加 Wistar rat[27] 85% P1 7 d 海马 Neu凋亡增加 Wistar rat[28] 85% P1 7 d 大脑皮层 — C57BL/6 WT mice[29] 85% P1 10 d 海马齿状回: 颗粒下区侧脑室: 脑室下区 NPCs增殖减少、凋亡增加 C57BL/6 WT mice(BPD)[6] 85% P1 14 d 总大脑体积减小，海马体积减小，脑室下区、海马齿状回亦受影响 NPCs增殖减少 Wistar rat[30] >85% P1 24 h/72 h/7 d 海马 海马锥体细胞体积、数量减少 C57BL/6 WT mice[31] 90% P0 7 d 前额叶皮层、顶叶皮层、海马 Neu凋亡增加; OLs髓鞘形成减少 Sprague-Dawley rat[32] 100% P14 7 d 海马 海马锥体细胞凋亡增加 Wistar rat[33] 100% P7 48 h 大脑皮质(主要累及，外侧明显); 海马、齿状回(轻微改变); 小脑(受累不明显); 中央白质(仅少量变性细胞) — FiO2: 吸入氧浓度; NPCs: 神经祖细胞; OPCs: 少突胶质前体细胞; OLs: 少突胶质细胞; AS: 星形胶质细胞; MG: 小胶质细胞; Neu: 神经元;
GCPs: 小脑颗粒细胞前体; PC: 浦肯野细胞; GABA: γ-氨基丁酸。
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表 1 高氧导致脑损伤动物模型及验证
动物 FiO2 高氧暴露开始时间 高氧暴露持续时间 脑损伤区域 损伤细胞及变化趋势 Wistar rat[14] 80% P6 24 h 脑白质、灰质丘脑、海马 OLs凋亡增加 Wistar rat[15] 80% P6 24 h 小脑 AS产生生长因子减少; OPCs增殖减少及成熟障碍; OLs凋亡增加 Wistar rat[16] 80% P6 24 h 小脑皮质 Neu: GCPs增殖及成熟减少、凋亡增加; PC树突形成延迟、分支减少 Wistar rat[17] 80% P6 24 h 脑白质: 外囊、胼胝体 OPCs增殖减少、成熟障碍、凋亡增加、髓鞘形成不足; MG活化 Wistar ratsynRas-transgenic mice[18] 80% P7 24 h 尾状核、伏隔核、额叶、顶叶、扣带、压后皮质、前脑内的白质束 Neu凋亡 Sprague-Dawley rat[19] 80% P6 24 h — Neu谷氨酸分泌增加，兴奋性毒性损伤 C57BL/6 WT mice[20] 80% P5 48 h 脑灰质 GABA能中间神经元功能损伤及成熟障碍 C57BL/6 WT mice[3] 80% P5 48 h 脑灰质 OLs神经营养因子表达减少、髓鞘形成减少; GABA能中间神经元成熟障碍及细胞损伤 Sprague-Dawley rat[21] 80% P6 48 h — — Wistar rat[22] 80% P3 48 h 脑白质 OPCs髓鞘形成不足 C57BL/6 WT mice[8] 80% P4 4 d 外囊、脑室下区、脑室周围区 外囊: OLs减少、毛细血管减少; 脑白质: AS增生; 脑室下区: 细胞凋亡增加; 脑室周围区: 毛细血管减少 Sprague-Dawley rat[23] 80% P1 6 d 脑灰质、海马 — — 80% P6 24 h — Neu兴奋性毒性损伤: 谷氨酸转运体表达下降，谷氨酸在突触间隙堆积[24] C57BL/6 WT mice[25] 80%~85% P6 48 h 海马 NPCs生成减少、凋亡增加; 中间神经元减少、树突分支减少 Wistar rat[26] 85% P1/P3/P7 24 h/72 h/7 d 脑灰质 Neu凋亡增加 Wistar rat[27] 85% P1 7 d 海马 Neu凋亡增加 Wistar rat[28] 85% P1 7 d 大脑皮层 — C57BL/6 WT mice[29] 85% P1 10 d 海马齿状回: 颗粒下区侧脑室: 脑室下区 NPCs增殖减少、凋亡增加 C57BL/6 WT mice(BPD)[6] 85% P1 14 d 总大脑体积减小，海马体积减小，脑室下区、海马齿状回亦受影响 NPCs增殖减少 Wistar rat[30] >85% P1 24 h/72 h/7 d 海马 海马锥体细胞体积、数量减少 C57BL/6 WT mice[31] 90% P0 7 d 前额叶皮层、顶叶皮层、海马 Neu凋亡增加; OLs髓鞘形成减少 Sprague-Dawley rat[32] 100% P14 7 d 海马 海马锥体细胞凋亡增加 Wistar rat[33] 100% P7 48 h 大脑皮质(主要累及，外侧明显); 海马、齿状回(轻微改变); 小脑(受累不明显); 中央白质(仅少量变性细胞) — FiO2: 吸入氧浓度; NPCs: 神经祖细胞; OPCs: 少突胶质前体细胞; OLs: 少突胶质细胞; AS: 星形胶质细胞; MG: 小胶质细胞; Neu: 神经元;
GCPs: 小脑颗粒细胞前体; PC: 浦肯野细胞; GABA: γ-氨基丁酸。
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