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CCK-8 inhibits expression of TNF-alpha in the spleen of endotoxic shock rats and signal transduction mechanism of p38 MAPK.
Meng, Ai-Hong; Ling, Yi-Ling; Zhang, Xiao-Peng; Zhao, Xiao-Yun; Zhang, Jun-Lan.
Affiliation
  • Meng AH; Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
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.
Subject(s)

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

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