Effects of Pentoxifylline Attenuates Septic Acute Lung Injury Induced by Cecal Ligation and Puncture on the Phosphorylation of p38 Mitogen Activated Protein Kinase and IκBα

OBJECTIVE To investigate the upstream signal transduction mechanism of pentoxifylline(PTX) on acute lung injury (ALI) in rats sepsis induced by intra-abdominal infection. METHODS SD rats were subjected to sepsis caused by cecal ligation and puncture(CLP), animals were randomly divided into sham operation group, sepsis group, sepsis+tragacanth group, sepsis+normal saline group, sepsis+SB203580 group, sepsis+PTX group. p38MAPK and IκBα phosphorylation were measured in 1, 3, 6, 12, 24 h respectively. And 1, 6, 24 h after pretreated with SB203580 or PTX, p38MAPK and IκBα phosphorylation, the concentration of plasma TNF-α, IL-6 were examined and the pulmonary histopathology after induced 24 h were determined. RESULTS Compared with sham operation group, p38MAPK and IκBα became phosphorylated and hence activated in sepsis group. Pretreated with both p38MAPK and IκBα were inhibited, consistent with the change of the concentration of plasma TNF-α, IL-6 and the pulmonary histopathology. CONCLUSION These results suggest that the inhibitory activity of pentoxifylline on the production of proinflammatory mediators and the pulmonary protection seems to be mediated via inhibition of p38MAPK and then suppression the activation of NF-κB in polymicrobial sepsis-induced ALI.