Anti-inflammatory effect of cholecystokinin and its signal transduction mechanism in endotoxic shock rat

Abstract

Aim: To study the anti-inflammatory effects of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS)-induced endotoxic shock (ES) and further investigate its signal transduction pathways involving p38 mitogen-activated protein kinase (MAPK) and IκB-α. Methods: Eighty-four rats were divided randomly into four groups: LPS (8 mg.kg-1, iv) induced ES; CCK-8 (40 μg.kg-1, iv) pretreatment 10 min before LPS (8 mg.kg-1); CCK-8 (40 μg.kg-1, iv) or normal saline (control) groups. The inflammatory changes of lung and spleen, phagocytic function of alveolar macrophage, quantification of inflammatory cells in bronchoalveolar lavage (BAL) were investigated in rats by using hematoxylin and eosin (HE) staining, phagocytosis of Candida albicans and differential cell counting. Nitric oxide (NO) production in serum, lung and spleen was measured with the Griess reaction. The mechanism involving p38 MAPK and IκB-α signal pathways was investigated by Western blot. Results: Inflammatory changes of lung and spleen induced by LPS were alleviated by CCK-8, the increase of NO induced by LPS in serum, lung and spleen was significantly inhibited and the neutrophil infiltration in BAL was significantly reduced by CCK-8. The number of neutrophils was (52±10)×106 cells.L-1 in LPS group, while it decreased to (18±4)×106 cells.L-1 in CCK-8+LPS (P<0.01). The phagocytic rate of CCK-8 group increased to (62.49±9.49) %, compared with control group (48.16±14.20) %, P<0.05. The phagocytosis rate was (85.14±4.64) % in LPS group, which reduced to (59.33±3.14) % in CCK-8+LPS group (P<0.01). The results of phagocytosis indexes showed similar changes. CCK-8 may play an important role in increasing the expression of p38 MAPK and decreasing the degradation of 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 MAPK and inhibition on the degradation of IκB-α.