摘要
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^(-1)in control group,while itincreased to(941±149)ng·L^(-1)in 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^(-1)inCCK-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.
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)-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 four groups of rats: LPS(S mg·kg^(-1),iv),CCK-8(40μg·kg^(-1),iv)pretreatment 10 rain before LPS(8 mg·kg^(-1)),CCK-8(40μg·kg^(-1),iv)or normal saline(control)group.The content of TNF-αin 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 p3S 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 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.
基金
the Health Committee of Hebei Province(No,2k002)
Science and Technology Department of Hebei Province(01276410D)
Natural Science Foundation of Hebei Province(No.302490)
