Application of Animal Models in Research on Hypoxia-Related Diseases
Abstract
Hypoxia-related diseases, such as altitude sickness, acute lung injury, and heart failure, have emerged as significant public health challenges worldwide and are strongly associated with increased mortality risks. These conditions tend to cause functional impairment and structural alterations in multiple organs, primarily due to inadequate oxygen supply or the inability of tissues to utilize oxygen effectively. To elucidate the pathophysiological mechanisms underlying hypoxia-associated diseases and to explore potential therapeutic strategies, researchers have employed animal models to conduct extensive mechanistic studies and drug development trials. In this review, we provide a comprehensive overview of the methods used to construct animal models for various hypoxia-related diseases. We made a thorough evaluation of the strengths, weaknesses, limitations, and applicability of each approach. In particular, we focus on modeling strategies for key pathologies such as altitude sickness, acute lung injury, pulmonary hypertension, and heart failure, discussing their respective advantages and restrains. Furthermore, we examined the potential application of gene editing technologies in optimizing animal models, especially its role in enhancing the accuracy and reproducibility of the models. The integration of these advanced technologies holds great promise for developing animal models with improved specificity and simulation of key features of diseases, which will serve as a solid foundation for basic research, drug screening, and preclinical trials concerning hypoxia-related diseases. Herein, we present a systematic summary and future outlook of animal models for hypoxia-related diseases, ultimately providing theoretical support for developing clinical treatment strategies and improving patient outcomes.
Keywords: Hypoxia, Animal models, Review
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RICHALET J P, HERMAND E, LHUISSIER F J. Cardiovascular physiology and pathophysiology at high altitude. Nat Rev Cardiol, 2024, 21(2): 75-88. doi: 10.1038/s41569-023-00924-9.
GATTERER H, VILLAFUERTE F C, ULRICH S, et al. Altitude illnesses. Nat Rev Dis Primers, 2024, 10(1): 43. doi: 10.1038/s41572-024-00526-w.
LI X, ZHANG J, LIU G, et al. High altitude hypoxia and oxidative stress: the new hope brought by free radical scavengers. Life Sci, 2024, 336: 122319. doi: 10.1016/j.lfs.2023.122319.
LUKS A M, HACKETT P H. Medical conditions and high-altitude travel. N Engl J Med, 2022, 386(4): 364-373. doi: 10.1056/NEJMra2104829.
DEMARTINI C, GRECO R, ZANABONI A M, et al. Nitroglycerin as a comparative experimental model of migraine pain: from animal to human and back. Prog Neurobiol, 2019, 177: 15-32. doi: 10.1016/j.pneurobio. 2019.02.002.
XU Y, SA Y, ZHANG C, et al. A preventative role of nitrate for hypoxia-induced intestinal injury. Free Radic Biol Med, 2024, 213: 457-469. doi: 10.1016/j.freeradbiomed.2024.01.030.
SONG K, LING H, WANG L, et al. Lactobacillus delbrueckii subsp. bulgaricus alleviates acute injury in hypoxic mice. Nutrients, 2024, 16(10): 1465. doi: 10.3390/nu16101465.
YANG X, DONG X, LI J, et al. Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury. J Biochem Mol Toxicol, 2024, 38(1): e23606. doi: 10.1002/jbt.23606.
YANG Y, HAN C, SUN Y, et al. Effects of acute high-altitude exposure on morphology and function of retinal ganglion cell in mice. Invest Ophthalmol Vis Sci, 2024, 65(10): 19. doi: 10.1167/iovs.65.10.19.
BERENDSEN R R, BÄRTSCH P, BASNYAT B, et al. Strengthening altitude knowledge: a Delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt Med Biol, 2022, 23(4): 330-337. doi: 10.1089/ham.2022.0083.
HAN R, YANG X, JI X, et al. Remote ischemic preconditioning prevents high-altitude cerebral edema by enhancing glucose metabolic reprogramming. CNS Neurosci Ther, 2024, 30(9): e70026. doi: 10.1111/cns.70026.
JIANG X, GAO J, FEI X, et al. Global profiling of protein lactylation in microglia in experimental high-altitude cerebral edema. Cell Commun Signal, 2024, 22(1): 374. doi: 10.1186/s12964-024-01748-x.
GARRIDO E, BOTELLA De MAGLIA J, CASTILLO O. Acute, subacute and chronic mountain sickness. Rev Clin Esp, 2020, S0014-2565(20): 30064-3. doi: 10.1016/j.rce.2019.12.013.
XU Y, LI H, SUN N, et al. Dry Powder formulations for inhalation require a smaller aerodynamic diameter for usage at high altitude. J Pharm Sci, 2023, 112(10): 2655-2666. doi: 10.1016/j.xphs.2023.08.009.
WANG Y, YIN Y, LIU Y, et al. Notoginsenoside R1 treatment facilitated Nrf2 nuclear translocation to suppress ferroptosis via Keap1/Nrf2 signaling pathway to alleviated high-altitude myocardial injury. Biomed Pharmacother, 2024, 175: 116793. doi: 10.1016/j.biopha.2024.116793.
MA R, ZHAO X, ZHAO J, et al. PrG protects postovulatory oocytes aging in mice through the putrescine pathway. Biochem Biophys Res Commun, 2024, 733: 150350. doi: 10.1016/j.bbrc.2024.150350.
GAO J, GUO Z, ZHAO M, et al. Lipidomics and mass spectrometry imaging unveil alterations in mice hippocampus lipid composition exposed to hypoxia. J Lipid Res, 2024, 65(7): 100575. doi: 10.1016/j.jlr. 2024.100575.
DAI S, FENG Y, LU C, et al. Impairment of autophagic flux after hypobaric hypoxia potentiates oxidative stress and cognitive function disturbances in mice. Neurosci Bull, 2024, 40(1): 35-49. doi: 10.1007/s12264-023-01099-6.
YAN C, WANG Z, LIU W, et al. Resveratrol ameliorates high altitude hypoxia-induced osteoporosis by suppressing the ros/hif signaling pathway. Molecules, 2022, 27(17): 5538. doi: 10.3390/molecules27175538.
GORMAN E A, O'KANE C M, MCAULEY D F. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management. Lancet, 2022, 400(10358): 1157-1170. doi: 10.1016/S0140-6736(22)01439-8.
CHEN Q H, ZHANG Y, GU X, et al. Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor. World J Stem Cells, 2024, 16(8): 811-823. doi: 10.4252/wjsc.v16.i8.811.
SHAH D, ROMERO F, STAFSTROM W, et al. Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury. Am J Physiol Lung Cell Mol Physiol, 2014, 306: 152-161. doi: 10.1152/ajplung.00229.2013.
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