Published online Feb 15, 2002. doi: 10.3748/wjg.v8.i1.139
Revised: November 23, 2001
Accepted: December 8, 2001
Published online: February 15, 2002
AIM: To study the effect of sulfated cholecystokinin-octapeptide (CCK-8) on systemic hypotension, gene and protein expression of TNF-α in spleen of lipopolysaccharide (LPS) nduced endotoxic shock (ES) rats, and further investigate the signal transduction mechanism of p38 mitogen-activated protein kinase (MAPK).
METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8 mg·kg- 1, iv), 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) group. The content of TNF-α in the spleen was assayed 2 h after LPS administration using ELISA kit and the expression of TNF-α mRNA was examined 30 min, 2 h and 6 h after LPS administration by reverse transcribed polymerase chain reaction (RT-PCR). Activation of p38 MAPK was detected with Western blot 30 min after LPS administration.
RESULTS: CCK-8 reversed LPS-induced decrease of mean arterial pressure ( MAP ) in rats. The content of TNF-α in the spleen was (282 ± 30) ng·L-1 in control group, while it increased to (941 ± 149) ng·L-1 in LPS group, P < 0.01. CCK-8 significantly inhibited the LPS-induced increase of TNF-α content in spleen. It decreased to (462 ± 87) ng·L-1 in CCK-8 + LPS group, P < 0.01. The expression of TNF-α mRNA 30 min and 2 h after treatment was stronger in LPS group, while it was lowered after CCK-8 pretreatment.The p38 MAPK expression increased significantly in LPS group (5.84 times of control) and CCK-8 increased the activation of p38 MAPK in ES rats (10.74 times of control).
CONCLUSION: CCK-8 reverses the decrease of MAP in ES rats and has inhibitory effect on the gene and protein expression of TNF-α in spleen, and p38 MAPK may be involved in its signal transduction mechanisms.