Institute of Brain Diseases and Cognition, Medical College of Xiamen University, Xiamen 361102, China.
Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
Int J Mol Sci. 2021 Jun 23;22(13):6705. doi: 10.3390/ijms22136705.
Hypoxia is associated with clinical diseases. Extreme hypoxia leads to multiple organs failure. However, the different effects of hypoxia on brain and visceral organs still need to be clarified, and moreover, characteristics in vulnerable organs suffering from hypoxia remain elusive. In the present study, we first aimed to figure out the hypoxic sensitivity of organs. Adult male mice were exposed to 6% O or 8% O for 6 h. Control mice were raised under normoxic conditions. In vivo and in vitro imaging of anti-HIF-1α-NMs-cy5.5 nanocomposites showed that the expression level of hypoxia-inducible factor (HIF-1α) was the highest in the liver, followed by kidney and brain. HIF-1α was detected in the hepatocytes of liver, distal convoluted tubules of kidney and neurons of cerebral cortex. The liver, kidney and brain showed distinct metabolic profiles but an identical change in glutamate. Compared with kidney and brain, the liver had more characteristic metabolites and more disturbed metabolic pathways related to glutaminolysis and glycolysis. The level of O-phosphocholine, GTP, NAD and aspartate were upregulated in hypoxic mice brain, which displayed significant positive correlations with the locomotor activity in control mice, but not in hypoxic mice with impaired locomotor activities. Taken together, the liver, kidney and brain are the three main organs of the body that are strongly respond to acute hypoxia, and the liver exhibited the highest hypoxic sensitivity. The metabolic disorders appear to underlie the physiological function changes.
缺氧与临床疾病有关。极度缺氧会导致多器官衰竭。然而，缺氧对大脑和内脏器官的不同影响仍需阐明，此外，易受缺氧影响的器官的特征仍难以捉摸。在本研究中，我们首先旨在确定器官对缺氧的敏感性。成年雄性小鼠暴露于 6% O 或 8% O 中 6 小时。对照组小鼠在常氧条件下饲养。抗 HIF-1α-NMs-cy5.5 纳米复合材料的体内和体外成像显示，肝脏中缺氧诱导因子 (HIF-1α) 的表达水平最高，其次是肾脏和大脑。在肝实质细胞、肾远曲小管和大脑皮质神经元中检测到 HIF-1α。肝脏、肾脏和大脑表现出不同的代谢特征，但谷氨酸的变化相同。与肾脏和大脑相比，肝脏具有更多特征代谢物和更多与谷氨酰胺分解和糖酵解相关的代谢途径紊乱。缺氧小鼠大脑中的 O-磷酸胆碱、GTP、NAD 和天冬氨酸水平上调，与对照组小鼠的运动活性呈显著正相关，但与运动活性受损的缺氧小鼠无关。总之，肝脏、肾脏和大脑是对急性缺氧强烈反应的三个主要身体器官，肝脏表现出最高的缺氧敏感性。代谢紊乱似乎是生理功能变化的基础。
