Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China.
Department of Aerospace Physiology, Air Force Medical University, Xi'an, China.
BMC Genomics. 2023 May 10;24(1):251. doi: 10.1186/s12864-023-09309-1.
With the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.
随着对极高海拔（HA）进入需求的增加，快速适应极度缺氧环境是我们需要探索的挑战。禁食被用于评估 HA 中的急性缺氧耐受性，并已被证明是提高极端 HA 生存率的有效方法。我们的实验还表明，禁食预处理 72 小时可显著提高 7620 米处大鼠 24 小时的存活率，从 10%提高到 85%，并保护大鼠的心肌细胞。在这里，我们比较了在正常海拔和极端 HA 下禁食和不禁食的 SD 大鼠心肌中的代谢物和基因表达。我们的研究结果表明，不同大鼠组之间检测到的差异代谢物（DM）的动态含量与差异表达基因（DEG）的表达一致，DM 簇与 DEG 簇也具有很强的相关性。禁食组的氨基酸和脂质相关 DM 簇明显降低，相关的 DEG 簇富集于有丝分裂途径，包括 CDK1、CDC7、NUF2 和 MCM6，表明禁食可以减弱心肌组织的有丝分裂过程，减少氨基酸和脂质的合成。没有预处理时，L-谷氨酰胺相关代谢物在极端 HA 下特别低，但在禁食组中正常。与 L-谷氨酰胺相关代谢物相关的簇中的 DEG 富集于 T 细胞受体 V(D)J 重组、Hippo 信号通路、Wnt 信号通路、cGMP-PKG 信号通路和 mTOR 信号通路，并显著下调，表明 L-谷氨酰胺的含量在极端 HA 下降低，而禁食则增加了它以适应环境。此外，在没有预处理的情况下，大鼠暴露于极端 HA 时检测到大量脂肪酸。我们的研究揭示了 SD 大鼠在禁食和低氧环境下的相关因素，并为心肌中的遗传和分子特征提供了新的见解，这对于开发更多潜在的极端 HA 快速适应方法至关重要。
