CCK-8 inhibits expression of TNF-α in the spleen of endotoxic shock rats and sigual transduction mechanism of p38 MAPK

AIM:To study the effect of sulfated cholecystokinin-octapeptide(CCK-8)on systemic hypotension,gene andprotein expression of TNF-α in spleen of lipopolysaccharide(LPS)-induced endotoxic shock(ES)rats,and furtherinvestigate the signal transduction mechanism of p38mitogen-activated protein kinase(MAPK).METHODS:The changes of blood pressure were observedusing physiological record instrument in four groups of rats:LPS(S mg·kg-1,iv),CCK-8(40μg·kg-1,iv)pretreatment10 rain before LPS(8 mg·kg-1),CCK-8(40μg·kg-1,iv)ornormal saline(control)group.The content of TNF-αinspleen was assayed 2 h after LPS administration usingELISA kit and the expression of TNF-α mRNA was examined30 min,2 h and 6 h after LPS administration by reversetranscribed polymerase chain reaction(RT-PCR).Activationof p3S MAPK was detected with Western blot 30 min afterLPS administration.RESULTS:CCK-8 reversed LPS-induced decrease of meanarterial pressure(MAP)in rats.The content of TNF-α inspleen was(282±30)ng·L-1in control group,while itincreased to(941±149)ng·L-1in LPS group,P<0.01.CCK-8 significantly inhibited the LPS-induced increase ofTNF-α content in spleen.It decreased to(462±87)ng·L-1inCCK-8+LPS group,P<0.01.The expression of TNF-αmRNA 30 min and 2 h after treatment was stronger in LPSgroup,while it was lowered after CCK-8 pretreatment.Thep38 MAPK expression increased significantly in LPS group(5.84 times of control)and CCK-8 increased the activationof p38 MAPK in ES rats(10.74 times of control).CONCLUSION:CCK-8 reverses the decrease of MAP in ESrats and has inhibitory effect on the gene and proteinexpression of TNF-α in spleen,and p38 MAPK may beinvolved in its signal transduction mechanisms.