[Inhibitory effect of cholecystokinin-octapeptide on production of cytokines in the lung of endotoxic shock rats].
To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in serum and lung of endotoxic shock (ES) rats induced by lipopolysaccharide (LPS) and investigate its signal transduction mechanism of p38 mitogen-activated protein kinase (MAPK), the changes in mean arterial pressure (MAP) were observed by using a polygraph in four groups of SD rats: group of LPS (8 mg/kg i.v.) induced ES, group of CCK-8 (40 microg/kg i.v.) pretreatment 10 min before LPS (8 mg/kg) administration, group of CCK-8 (40 microg/kg i.v.) only, and normal saline (control) group; the contents of proinflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in the lung and serum were assayed using ELISA kits; and p38 MAPK was detected by Western blot. The results showed that CCK-8 alleviated LPS-induced decrease in MAP of rats; compared with the control, LPS elevated the levels of TNF-alpha, IL-1 beta and IL-6 in serum and lung significantly, while CCK-8 significantly inhibited the LPS-induced increases in TNF-alpha, IL-1 beta and IL-6 in serum and lung. The activation of p38 MAPK in the lung of ES rats was enhanced by CCK-8 pretreatment. These results suggest that CCK-8 can alleviate the LPS-induced decrease in MAP of ES rats and exert an inhibitory effect on the overproduction of proinflammatory cytokines, and that p38 MAPK may be involved in its signal transduction mechanisms.
Meng
Ai-Hong
AH
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017.
Ling
Yi-Ling
YL
Zhao
Xiao-Yun
XY
Zhang
Jun-Lan
JL
Wang
Qiu-Hong
QH
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D016207:Cytokines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D012844:Sincalide