Anti-intlammatory effect of cholecystokinin ana its signal transduction mechanism in endotoxic shock rat

AIM:To study the anti-inflammatory effects ofcholecystokinin-octapeptide(CCK-8)onlipopolysaccharide(LPS)-induced endotoxic shock(ES)and further investigate its signal transduction pathwaysinvolving p38 mitogen-activated protein kinase(MAPK)and IκB-α.METHODS:Eighty-four rats were divided randomly intofour groups:LPS(8 mg·kg-1,iv)induced ES;CCK-8(40 μg·kg-1,iv)pretreatment 10 min before LPS(8mg·kg-1);CCK-8(40 μg·kg-1,iv)or normal saline(control)groups.The inflammatory changes of lung andspleen,phagocytic function of alveolar macrophage,quantification of inflammatory cells in bronchoalveolarlavage(BAL)were investigated in rats by usinghematoxylin and eosin(HE)staining,phagocytosis ofCandida albicans and differential cell counting.Nitricoxide(NO)production in serum,lung and spleen wasmeasured with the Griess reaction.The mechanisminvolving p38 MAPK and IκB-α signal pathways wasinvestigated by Western blot.RESULTS:Inflammatory changes of lung and spleeninduced by LPS were alleviated by CCK-8,the increaseof NO induced by LPS in serum,lung and spleen wassignificantly inhibited and the neutrophil infiltration inBAL was significantly reduced by CCK-8.The numberof neutrophils was(52±10)×10~6 cells·L-1in LPS group,while it decreased to(18±4)×10~6 cells·L-1in CCK-8+LPS(P<0.01).The phagocytic rate of CCK-8 groupincreased to(62.49±9.49)%,compared with controlgroup(48.16±14.20)%,P<0.05.The phagocytosisrate was(85.14±4.64)% in LPS group,which reducedto(59.33±3.14)% in CCK-8+LPS group(P<0.01).Theresults of phagocytosis indexes showed similar changes.CCK-8 may play an important role in increasing theexpression of p38 MAPK and decreasing the degradationof IκB-α in lung and spleen of ES rats.CONCLUSION:CCK-8 can result in anti-inflammatory effects,which may be related to activation of p38 MAPKand inhibition on the degradation of IκB-α.