Okazaki Kaoru, Nakamura Shinji, Koyano Kosuke, Konishi Yukihiko, Kondo Masatoshi, Kusaka Takashi
Department of Neonatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
Department of Pediatrics, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Front Pediatr. 2023 Jan 27;11:1070743. doi: 10.3389/fped.2023.1070743. eCollection 2023.
Neonatologists resuscitate asphyxiated neonates by every available means, including positive ventilation, oxygen therapy, and drugs. Asphyxiated neonates sometimes present symptoms that mimic those of inflammation, such as fever and edema. The main pathophysiology of the asphyxia is inflammation caused by hypoxic-ischemic reperfusion. At birth or in the perinatal period, neonates may suffer several, hypoxic insults, which can activate inflammatory cells and inflammatory mediator production leading to the release of larger quantities of reactive oxygen species (ROS). This in turn triggers the production of oxygen stress-induced high mobility group box-1 (HMGB-1), an endogenous damage-associated molecular patterns (DAMPs) protein bound to toll-like receptor (TLR) -4, which activates nuclear factor-kappa B (NF-κB), resulting in the production of excess inflammatory mediators. ROS and inflammatory mediators are produced not only in activated inflammatory cells but also in non-immune cells, such as endothelial cells. Hypothermia inhibits pro-inflammatory mediators. A combination therapy of hypothermia and medications, such as erythropoietin and melatonin, is attracting attention now. These medications have both anti-oxidant and anti-inflammatory effects. As the inflammatory response and oxidative stress play a critical role in the pathophysiology of neonatal asphyxia, these drugs may contribute to improving patient outcomes.
新生儿科医生会采用一切可用手段对窒息新生儿进行复苏，包括正压通气、氧疗和药物治疗。窒息新生儿有时会出现类似炎症的症状，如发热和水肿。窒息的主要病理生理学机制是缺氧缺血再灌注引起的炎症。在出生时或围产期，新生儿可能遭受多次缺氧损伤，这会激活炎症细胞并产生炎症介质，导致释放大量活性氧（ROS）。这进而引发氧应激诱导的高迁移率族蛋白B1（HMGB-1）的产生，HMGB-1是一种与Toll样受体（TLR）-4结合的内源性损伤相关分子模式（DAMPs）蛋白，它会激活核因子-κB（NF-κB），导致产生过量的炎症介质。ROS和炎症介质不仅在活化的炎症细胞中产生，也在非免疫细胞如内皮细胞中产生。低温可抑制促炎介质。低温与药物如促红细胞生成素和褪黑素的联合治疗目前正受到关注。这些药物具有抗氧化和抗炎作用。由于炎症反应和氧化应激在新生儿窒息的病理生理学中起关键作用，这些药物可能有助于改善患者预后。
