Hypoxia inducible factor (HIF) is one of the major transcription factors through which cells and tissues adapt to hypoxic-ischemic injury. However, the specific mechanism by which HIF regulates amino acid metabolism and its effect on neurons during hypoxic ischemia (HI) have remained unclear. This study analyzed the changes in cerebral metabolism of amino acids after HI by using 1H-MRS and investigated the relationship between the changes in cerebral metabolism of amino acids and HIF-1α as well as the potential effects on neurons. Newborn pigs were used as an HI model in this study. Twenty-eight newborn Yorkshire pigs (male, 1.0-1.5 kg) aged 3-5 days were selected and randomly divided into experimental groups tested at 0-2 h (n = 4), 2-6 h (n = 4), 6-12 h (n = 4), 12-24 h (n = 4), 24-48 h (n = 4), and 48-72 h (n = 4) after HI, and a control group (n = 4). After the modeling was completed, 1H-MRS imaging was conducted, followed by immunohistochemical staining of HIF-1α, NeuN, and doublecortin (DCX), and immunofluorescence of glutamic oxaloacetic transaminase (GOT)-1, GOT2, glutathione synthase (GS), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) in brain tissues. The expression of HIF-1α exhibited two increases after HI injury. The first time was opposite to the trends of change of GOT2, aspartic acid, and the number of neurons, while the second was consistent with these trends, suggesting that HIF-1α may have a two-way induction effect on neurons by regulating GOT2 after HI. HIF-1α was closely related to GCLM expression, and GSH level was correlated with the number of hippocampal neurons, indicating that HIF-1α may regulate GCLM to promote GSH synthesis and additionally play a neuroprotective role.

中文翻译：

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缺氧缺血后 HIF-1α 与氨基酸代谢的潜在关系和对神经元的双重影响。

缺氧诱导因子（HIF）是细胞和组织适应缺氧缺血性损伤的主要转录因子之一。然而，HIF 调节氨基酸代谢的具体机制及其在缺氧缺血 (HI) 期间对神经元的影响仍不清楚。本研究采用1H-MRS分析HI后脑氨基酸代谢变化，探讨脑氨基酸代谢变化与HIF-1α的关系及其对神经元的潜在影响。在这项研究中，新生猪被用作 HI 模型。选取3-5日龄新生约克夏猪28头（雄性，1.0-1.5kg），随机分为实验组，分别在0-2h（n=4）、2-6h（n=4）、6 HI 后 -12 小时 (n = 4)、12-24 小时 (n = 4)、24-48 小时 (n = 4) 和 48-72 小时 (n = 4)，和一个对照组（n = 4）。造模完成后进行1H-MRS显像，HIF-1α、NeuN、双皮质素（DCX）免疫组化染色，谷氨酸草酰转氨酶（GOT）-1、GOT2、谷胱甘肽合成酶（GS）免疫荧光，脑组织中的谷氨酸-半胱氨酸连接酶催化亚基 (GCLC) 和谷氨酸-半胱氨酸连接酶修饰亚基 (GCLM)。HIF-1α的表达在HI损伤后表现出两次增加。第一次与GOT2、天冬氨酸、神经元数量变化趋势相反，第二次与这些趋势一致，表明HIF-1α可能通过调节GOT2后对神经元产生双向诱导作用。你好。HIF-1α与GCLM表达密切相关，GSH水平与海马神经元数量相关，