Morphological and molecular biological features of LPS-induced systemic inflammatory response were assessed in old male Wistar rats with high (HR) and low (LR) resistance to hypoxia. The systemic inflammatory response was modeled by intraperitoneal injection of E. coli O26:B6 LPS; the animals were sacrificed after 6 h. In histological sections, the number of neutrophils in the interalveolar septa and the area of necrosis in the liver were determined. The expression levels of Hif1a, Hif2a, Nfkb, Vegf, Il1b, Il6, Il10, and Tgfb mRNA in the liver and serum concentrations of HIF-1α and IL-1β were determined. In 4-6 h after LPS injection, 3 (43%) of 7 HR rats died, whereas no deaths were observed among LR rats. At 6 h after LPS injection, the number of neutrophils in the interalveolar septa of the lungs in LR rats was significantly higher than in HR rats, while the area of necrosis in the liver did not differ. At the same time, the mRNA expression levels of the proinflammatory cytokine genes Il1b and Il6 increased in the liver of both HR and LR rats, whereas the expression of Il10 increased only in HR rats. The expression of the Hif1a gene in the liver was higher in LR rats, but the content of HIF-1α protein in blood serum was higher in HR animals. These data should be taken into account when developing new approaches to the therapy of systemic inflammatory response in infectious and inflammatory diseases in the elderly.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Devraj G, Beerlage C, Brüne B, Kempf VA. Hypoxia and HIF-1 activation in bacterial infections. Microbes Infect. 2017;19(3):144-156. https://doi.org/10.1016/j.micinf.2016.11.003
Dzhalilova DS, Kosyreva AM, Diatroptov ME, Ponomarenko EA, Tsvetkov IS, Zolotova NA, Mkhitarov VA, Khochanskiy DN, Makarova OV. Dependence of the severity of the systemic inflammatory response on resistance to hypoxia in male Wistar rats. J. Inflamm Res. 2019;12:73-86. https://doi.org/10.2147/JIR.S194581
Jain K, Suryakumar G, Prasad R, Ganju L. Differential activation of myocardial ER stress response: a possible role in hypoxic tolerance. Int. J. Cardiol. 2013;168(5):4667-4677. https://doi.org/10.1016/j.ijcard.2013.07.180
Kirova YI, Germanova EL, Lukyanova LD. Phenotypic features of the dynamics of HIF-1α levels in rat neocortex in different hypoxia regimens. Bull. Exp. Biol. Med. 2013;154(6):718-722. https://doi.org/10.1007/s10517-013-2038-z
Kosyreva AM, Dzhalilova DS, Tsvetkov IS, Diatroptov ME, Makarova OV. Age-specific features of hypoxia tolerance and intensity of lipopolysaccharide-induced systemic inflammatory response in Wistar rats. Bull. Exp. Biol. Med. 2019;166(5):699-703. https://doi.org/10.1007/s10517-019-04421-3
Gaillard S, Dellasanta P, Loutan L, Kayser B. Awareness, prevalence, medication use, and risk factors of acute mountain sickness in tourists trekking around the Annapurnas in Nepal: a 12-year follow-up. High Alt. Med. Biol. 2004;5(4):410-419. https://doi.org/10.1089/ham.2004.5.410
Wu TY, Ding SQ, Liu JL, Jia JH, Chai ZC, Dai RC, Zhao JZ, Tang QD, Kayser B. Smoking, acute mountain sickness and altitude acclimatisation: a cohort study. Thorax. 2012;67(10):914-919. https://doi.org/10.1136/thoraxjnl-2011-200623
Kosyreva AM, Sentyabreva AV, Tsvetkov IS, Makarova OV. Alzheimer’s Disease and Inflammaging. Brain Sci. 2022;12(9):1237. https://doi.org/10.3390/brainsci12091237
Farshbafnadi M, Kamali Zonouzi S, Sabahi M, Dolatshahi M, Aarabi MH. Aging & COVID-19 susceptibility, disease severity, and clinical outcomes: The role of entangled risk factors. Exp. Gerontol. 2021;154:111507. https://doi.org/10.1016/j.exger.2021.111507.
Islam MT. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol. Res. 2017;39(1):73-82. https://doi.org/10.1080/01616412.2016.1251711
Belaiba RS, Bonello S, Zähringer C, Schmidt S, Hess J, Kietzmann T, Görlach A. Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells. Mol. Biol. Cell. 2007;18(12):4691-4697. https://doi.org/10.1091/mbc.e07-04-0391
Dzhalilova DS, Diatroptov ME, Tsvetkov IS, Makarova OV, Kuznetsov SL. Expression of Hif-1α, Nf-κb, and Vegf genes in the liver and blood serum levels of HIF-1α, Erythropoietin, VEGF, TGF-β, 8-Isoprostane, and Corticosterone in Wistar rats with high and low resistance to hypoxia. Bull. Exp. Biol. Med. 2018;165(6):781-785. https://doi.org/10.1007/s10517-018-4264-x
Zhao HQ, Li WM, Lu ZQ, Sheng ZY, Yao YM. The growing spectrum of anti-inflammatory interleukins and their potential roles in the development of sepsis. J. Interferon Cytokine Res. 2015;35(4):242-251. https://doi.org/10.1089/jir.2014.0119
Ono S, Tsujimoto H, Hiraki S, Aosasa S. Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis. Ann. Gastroenterol. Surg. 2018;2(5):351-358. https://doi.org/10.1002/ags3.12194
Slaats J, Ten Oever J, van de Veerdonk FL, Netea MG. IL-1β/IL-6/CRP and IL-18/ferritin: Distinct inflammatory programs in infections. PLoS Pathog. 2016;12(12):e1005973. https://doi.org/10.1371/journal.ppat.1005973
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 175, No. 5, pp. 650-656, May, 2023
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Dzhalilova, D.S., Silina, M.V., Kosyreva, A.M. et al. Morphological and Molecular Biological Features of the Systemic Inflammatory Response in Old Wistar Rats with High and Low Resistance to Hypoxia. Bull Exp Biol Med 175, 704–710 (2023). https://doi.org/10.1007/s10517-023-05930-y
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-023-05930-y