[cAMP response element binding protein expression and activity in acute lung injury induced by endotoxinemia following hemorrhagic shock: experiment with rabbits].

OBJECTIVE: To investigate the cAMP response element binding protein (CREB) expression and activity in acute lung injury induced by endotoxinemia following hemorrhagic shock.

METHODS: Thirty-six rabbits were randomly divided into 3 equal groups: 2 hours after the endotoxinemia following hemorrhagic shock group that underwent exsanguination, injected intraperitoneally with lipopolysaccharide (LPS) after the blood pressure became stable, and then underwent extraction of carotid blood for blood gas test and killed 2 hours later; 12 hours after the endotoxinemia following hemorrhagic shock (two hits) group: undergoing the above mentioned management and being killed 12 hours later; and control group, undergoing sham operation. The lungs were taken out to undergo histological examination. The partial arterial blood pressure of oxygen (PaO2) and wet lung weight to dry lung weight ratio (W/D) were measured. The concentration of tumor necrosis factor (TNF)-alpha in the lung homogenate was measured by enzyme-linked immunosorbent assay (ELISA). The expression of CREB in the lung was assessed by Western blotting and the CREB/DNA binding activity was assayed with electrophoretic mobility shift assay (EMSA).

RESULTS: Pathological examination of the lung tissues showed that the alveolar structures were severely destroyed and large number of WBC infiltrating in both alveolar sacs and pulmonary interstitial with RBC leakage the 12 hours after the endotoxinemia following hemorrhagic shock group, and the changes were mild in the 2 hours after two hits group. The PaO2 was significantly reduced in the 12 hour after endotoxinemia following hemorrhagic shock group compared with the control group (P < 0.01). The lung W/D and the concentration of TNF-alpha in lung homogenate were significantly increased in the 12 hours after endotoxinemia following hemorrhagic shock group compared with the control group (both P < 0.01). Nevertheless there were not significant differences in the PaO2, W/D and TNF-alpha between the 2 hours after two hits group and the control group. The expression level and DNA binding activity of CREB in the lung were significantly higher in both 2 and 12 hours after endotoxinemia following hemorrhagic shock groups than those in the control group (all P < 0.01).

CONCLUSION: CREB in the lung is activated by endotoxinemia following hemorrhagic shock and may participate in the inflammatory response in acute lung injury by regulating the expression of inflammatory factors.