Kosyreva A.M.1, Dzhalilova D.Sh.1, Tsvetkov I.S.1, Diatroptov M.E.1, Makarova O.V.1
1 Sience Research Institute of Human Morphology, Laboratory of immunomorphology of inflammation, Moscow, Russia
Hypoxia contributes to the development of inflammation, since the signaling pathways activated by hypoxia, are closely related to inflammatory ones. However, there are no data about the relationship of age-related resistance to hypoxia and the severity of inflammation.
The aim was to study the relationship between resistance to hypoxia and the severity of the systemic inflammatory response (SIR) induced by the high-dose of LPS administration in male Wistar rats of different age groups.
Three age groups of male Wistar rats were used: newborns, prepubescent, sexually mature. To assess sensitivity to hypoxia, animals were placed in a pressure chamber at a height of 11,500 m. The SIR was modeled by intraperitoneal injection of E.coli O26:B6 LPS. One day after the LPS administration the serum levels of HIF-1α, neopterin, C-reactive protein were measured by ELISA. The level of endotoxin in serum was determined by the LAL-test. Alterative changes were evaluated in histological sections of the liver. Statistical analysis was carried out in the “Statistica 8.0” using the criteria of multiple comparison of Kruskal–Wallis and Dann.
An estimate of the lifetime in the pressure chamber showed that prepubescent animals are predisposed to hypoxia. In the serum of prepubescent rats of the control group, the content of HIF-1α was the lowest than in other ages. Compared with newborns and adults, LPS administration in prepubescent animals showed the most pronounced alterative changes in the liver, an increase endotoxin, neopterin, C-reactive protein. The less pronounced SIR were found in newborns, which correlates with their high resistance to hypoxia.
Thus, in the prepubescent period, male Wistar rats are highly susceptible to hypoxia, and the administration of LPS induced a severe course of SIR. These data must be taken into account when developing approaches to the therapy of infectious and inflammatory diseases in prepubescent children.
Doctoral School: Hystology, cytology and cell biology
Program: Sex differences of systemic inflammatory response syndrome (SIRS)
Supervisor: Olga V. Makarova
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