Institute of Medicine and Hygienic Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China.
Key Laboratory of High Altitude Medicine, Ministry of Education, College of High Altitude Military Medicine, Third Military Medical University, Chongqing 400038, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6828-6836. doi: 10.3892/mmr.2017.7493. Epub 2017 Sep 13.
Hypoxic preconditioning (HPC) is well‑known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.
低氧预适应（HPC）众所周知可发挥抗低氧损伤的保护作用；然而，其潜在的分子机制尚不清楚。本研究采用血清代谢组学方法来检测与 HPC 相关的变化。在本研究中，通过使成年 BALB/c 小鼠四次暴露于急性重复低氧中来建立 HPC 动物模型。通过眼眶采血来收集血清样本。采用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-QTOFMS）进行代谢物谱分析，并结合单变量和多变量统计分析。本研究的结果证实 HPC 小鼠模型建立并得到了优化，提示在分子水平上对照组和 HPC 组之间存在显著差异。HPC 导致显著的代谢改变，表现为缬氨酸、蛋氨酸、酪氨酸、异亮氨酸、苯丙氨酸、溶血磷脂酰胆碱（LysoPC；16:1）、LysoPC（22:6）、亚麻酰肉碱、棕榈酰肉碱、十八烯酰肉碱、牛磺酸、花生四烯酸、亚油酸、油酸和棕榈酸的显著上调，以及乙酰肉碱、苹果酸、柠檬酸和琥珀酸的显著下调。使用 MetaboAnalyst 3.0，观察到许多关键代谢途径被急性扰乱，包括缬氨酸、亮氨酸和异亮氨酸生物合成，以及牛磺酸、次牛磺酸、苯丙氨酸、亚油酸和花生四烯酸代谢。本研究的结果为生物体对低氧适应的机制提供了新的见解，并证明了 HPC 的保护机制。
