中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 788-790.doi: 10.4103/1673-5374.322459

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

乳酸盐在新生儿缺氧缺血性脑病治疗中的潜在用途

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Potential use of lactate for the treatment of neonatal hypoxic-ischemic encephalopathy

Isadora D’Ávila Tassinari, Luciano Stürmer de Fraga*   

  1. Laboratory of Neurobiology and Metabolism (NeuroMet), Department of Physiology, Instituto de Ciências Básicas da Saúde (ICBS), Federal University of Rio Grande do Sul (UFRGS); Post-Graduate Program in Physiology, Instituto de Ciências Básicas da Saúde (ICBS), Federal University of Rio Grande do Sul (UFRGS); Unidade de Experimentação Animal, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Luciano Stürmer de Fraga, lucianof@ufrgs.br.
  • Supported by:
    Studies from our research group over the years have received funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS-Brazil) and Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA-Brazil) (to LSdeF).

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摘要： Neural Regen Res：缺氧缺血性脑病后乳酸盐介导的神经保护作用
   乳酸盐是由糖酵解代谢产生的三碳分子，是一种代谢废物，在临床治疗中没有任何用途。然而，乳酸盐现在被公认为一种潜在的能量底物，也是一种抗炎信号分子。这些功能首次在成年动物模型中报告，包括脑损伤和脑缺血，并且也在人类患者中观察到。腹腔注射乳酸能够到达大脑，有助于减少脑损伤，以及改善行为参数。尽管临床前研究是用新生大鼠进行的，但乳酸盐有可能作为临床治疗缺氧缺血性脑病的药物。缺氧缺血性脑病是一种仍影响大量新生儿的疾病。为了减轻缺氧缺血性脑病的有害影响，减少不良的长期神经后果，治疗性低温是缺氧缺血性脑病患儿的标准治疗方法。但是，这有一些局限性，例如治疗窗口短。将治疗与治疗性低温结合起来的时机仍然是缺氧缺血性脑病护理值得讨论的话题。细致的诊断对于适当的神经保护治疗也很重要。研究乳酸盐在不同脑细胞中的作用方式将为缺氧缺血性脑病的治疗奠定基础。
    来自巴西南里奥格兰德州联邦大学的Luciano Sturmer de Fraga团队认为在使用乳酸盐治疗人类婴儿缺氧缺血性脑病之前，需要遵循一些重要的步骤。在临床试验中测试乳酸盐治疗之前，应对大型动物（如仔猪和母羊）进行临床前研究，并测试不同剂量和给药方案。动物模型已成功表明治疗性低温可用于治疗缺氧缺血性脑病。在动物模型中结合乳酸盐给药和治疗性低温（缺氧缺血性脑病的标准临床治疗）的研究将有助于进一步分析。这是一个从动物模型到临床，从工作台到床的转化研究的例子。尽管有一些局限性，但已经拯救了数百万人的生命。大脑是一个需要能量的器官，它的结构和生理过程需要仔细的分配，有许多不同的细胞类型和代谢特征。缺氧缺血性脑病是一种导致神经损伤的疾病，与窒息的早期阶段有关，因此与能量衰竭机制有关。缺氧缺血性脑病影响许多新生儿，但也影响他们的家庭和生活方式。考虑到乳酸盐对新生儿及其家人的健康和生活质量的改善，乳酸盐可能是缺氧缺血性脑病治疗的一个有希望的策略。  
    文章在《中国神经再生研究（英文版）》杂志2022年 4 月  4 期发表。


https://orcid.org/0000-0001-7203-3467 (Luciano Stürmer de Fraga) 

Abstract: Function of lactate: Lactate is a three-carbon molecule produced by glycolytic metabolism that is a metabolic waste product with no known use in clinical therapy. Conversely, it is a metabolite that the body should quickly guarantee the clearance. However, lactate is now recognized as a potential energy substrate, as well as an anti-inflammatory signaling molecule. These actions were first reported in adult animal models with a brain injury, including a traumatic brain injury and cerebral ischemia, and have also been observed in human patients (Magistretti and Allaman, 2018). Recently, however, two studies by independent research groups described promising neuroprotective results from the use of lactate in animal models with neonatal hypoxia-ischemia (Roumes et al., 2021; Tassinari et al., 2020). Both studies suggested that lactate administered intraperitoneally was able to reach the brain and contribute to the reduction of brain injury, as well as improve behavioral parameters. Despite that the pre-clinical studies were performed using neonatal rats, they suggest the potential use of lactate as clinical therapy for the treatment of hypoxic-ischemic encephalopathy (HIE), a disorder still affecting a high number of newborns.