| Sepsis, a leading cause of death in patients with critical illness, has been defined as a syndrome mainly characterized by a systemic inflammatory response induced by infection, with a morbidity of about 8.68% and mortality of about 48.7% in China. Up to now, the emergency management of sepsis is mainly early goal-directed therapy. We have demonstrated that 100% oxygen inhalation is beneficial to zymosan-induced generalized inflammation, and reactive oxygen species (ROS) may be involved in the protection of oxygen treatment. Other investigators suggest that ROS may modulate the sympathetic nerve system activity and beta2-adrenergic receptor (β2AR) mediated pathway. Moreover, studies have demonstrated thatβ2AR agonists are beneficial to sepsis. Therefore, we assessed the effects ofβ2AR antagonist butoxamine on the protection of oxygen treatment against zymosan-induced generalized inflammation in mice, as well as the role of cAMP.Materials and methodsWe used male Imprinting Control Region mice (Specific Pathogen Free) weighing 20 to 25 grams for the study. Animals were randomly assigned to the following groups: Normal saline+Air, Zymosan+Air, Zymosan+Oxygen, Zymosan+Oxygen+Butoxamine, Zymosan+Air+Butoxamine and Normal saline+Air+Butoxamine groups. Generalized inflammation was induced by intraperitoneal injection with 1 g/kg of a sterile suspension of zymosan. Mice were given oxygen treatment by exposure to 100% oxygen for 3 hours starting at 4 and 12 hours after the zymosan injection respectively.β2AR antagonist butoxamine (5mg/kg) was intraperitoneally injected 30 minutes prior to inhaling 100% oxygen. In the mortality study, survival was monitored for 7 days after zymosan injection in mice. At 24 hours after the zymosan injection, mice were given euthanasia, and blood sample and organs were harvested for determining the histopathologic analysis, levels of lactate dehydrogenase (LDH), C reactive protein (CRP), arterial blood gas analysis, inflammatory cytokines as well as cAMP.ResultsWe observed that zymosan induced abnormal changes in organ histopathology, LDH and CRP in serum, inflammatory cytokines in serum and tissue, and arterial blood gases analysis, as well as the lower survival rate in zymosan-challenged mice, which were prevented by 100% oxygen treatment. We found that pretreatment withβ2AR antagonist butoxamine partly abolished the protection of 100% oxygen inhalation. We also showed that zymosan induced the increase of serum cAMP and the decrease of tissue cAMP. However, oxygen treatment increased the cAMP levels in both serum and tissue, which were partly abolished by pretreatment with butoxamine. Conclusion100% oxygen inhalation may protect against zymosan-induced generalized inflammation in mice partly through activation ofβ2AR pathway, and subsequently enhancing the cAMP levels in both serum and tissue. |
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