Recombinant CC16 regulates inflammation, oxidative stress, apoptosis and autophagy via the inhibition of the p38MAPK signaling pathway in the brain of neonatal rats with sepsis.

Sepsis has a high in clinic neonatal mortality. Moreover, a considerable number of children's brains remain affected even after the treatment of sepsis and it often leaves sequelae. Therefore, early intervention for sepsis is of considerable significance. Recent studies have shown that Club cell protein (CC16) is closely related to the p38 mitogen-activated protein kinase (MAPK) signaling pathway, which can regulate inflammation, oxidative stress, apoptosis, and autophagy during sepsis. Thus, we analyzed the neuroprotective effect of recombinant CC16 (rCC16) in a neonatal sepsis rat model. For the first time, we found that the p38MAPK signaling pathway was activated in neonatal brain tissue of rats with sepsis, and the CC16 levels decreased significantly. Secondly, after the rCC16 interference, the occurrence of inflammation, oxidative stress and apoptosis were subsequently reversed, and autophagy was further stimulated. Finally, through further intervention using the p38MAPK signaling pathway inhibitor, SB203580, or its agonist, anisomycin, we confirmed that rCC16 reduced rat mortality and improve general conditions. Simultaneously, it had also neuroprotective effect. Its mechanism could be related to oxidative stress, inflammation, and apoptosis reduced and autophagy activated by rCC16 inhibiting the p38MAPK signaling pathway. Taken together, these findings provide insight into the pathogenesis, prevention, and treatment of sepsis via the activity of rCC16.