CCK-8 inhibits expression of TNF-alpha in the spleen of endotoxic shock rats and signal transduction mechanism of p38 MAPK.
World J Gastroenterol
; 8(1): 139-43, 2002 Feb.
Article
in En
| MEDLINE
| ID: mdl-11833090
ABSTRACT
AIM:
To study the effect of sulfated cholecystokinin-octapeptide (CCK-8) on systemic hypotension, gene and protein expression of TNF-alpha in the spleen of lipopolysaccharide (LPS)-induced 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 the four groups of rats LPS (8 mg x kg(-1), iv), CCK-8 (40 microg x kg(-1), iv) pretreatment 10 min before LPS (8 mg x kg(-1)), CCK-8 (40 microg x kg(-1), iv) or normal saline (control) group. The content of TNF-alpha in the spleen was assayed 2 h after LPS administration using ELISA kit and the expression of TNF-alpha 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-alpha in the spleen was (282+/-30) ng x L(-1) in control group, while it increased to (941+/-149) ng x L(-1) in LPS group, P<0.01. CCK-8 significantly inhibited the LPS-induced increase of TNF-alpha content in spleen. It decreased to (462 +/-87) ng x L(-1) in CCK-8+LPS group, P<0.01. The expression of TNF-alpha 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-alpha in spleen, and p38 MAPK may be involved in its signal transduction mechanisms.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sincalide
/
Tumor Necrosis Factor-alpha
/
Endotoxemia
/
Mitogen-Activated Protein Kinases
/
MAP Kinase Signaling System
Limits:
Animals
Language:
En
Journal:
World J Gastroenterol
Journal subject:
GASTROENTEROLOGIA
Year:
2002
Type:
Article
Affiliation country:
China