Durán Fernández-Feijóo Cristina, Rodríguez-Fanjul Javier, Lopez-Abat Miriam, Hadley Stephanie, Cavia-Saiz Mónica, Muñiz Pilar, Arnaez Juan, Fernández-Lorenzo José Ramón, Camprubí Camprubí Marta
Department of Neonatology, Hospital Álvaro Cunqueiro, EOXI, 36312 Vigo, Spain.
Neonatal Intensive Care Unit, Paediatrics Department, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, 08916 Badalona, Spain.
Antioxidants (Basel). 2021 Sep 25;10(10):1523. doi: 10.3390/antiox10101523.
Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2α was measured in brain tissue. Plasma 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE.
尽管进行了低温治疗，但缺氧缺血性脑病（HIE）仍是新生儿期发病和死亡的主要原因之一。有证据表明，氧化损伤在缺氧缺血性（HI）脑损伤的病理生理学中起重要作用。我们的目的是研究出生后给予别嘌醇联合低温治疗是否会降低HIE动物模型中的氧化应激（OS）生物标志物。出生10天的大鼠幼崽接受中度严重程度的单侧HI。幼崽被随机分为：假手术组、缺氧缺血组（HI）、HI + 别嘌醇组（HIA）、HI + 低温组（HIH）和HI + 低温 + 别嘌醇组（HIHA）。评估了OS和抗氧化剂的生物标志物：检测了血浆中的谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值和羰基。分析了血浆和脑脊液中的总抗氧化能力（TAC），并测量了脑组织中的8-异前列腺素F2α。接受别嘌醇和双重治疗的组血浆2,2'-偶氮二（3-乙基苯并噻唑啉-6-磺酸）（ABTS）水平保持不变。在脑脊液中，只有HIA组血浆铁还原能力（FRAP）水平正常。在接受低温和别嘌醇治疗的所有组中，蛋白质氧化和脂质过氧化均显著降低，从而增强了对HIE的神经保护作用。
