CCK-8对内毒素休克大鼠肺脏细胞因子的抑制效应

观察八肽胆囊收缩素(cholecystokinin-octapeptide,CCK-8）改善脂多糖(lipopolysaccharide,LPS）引起的大鼠内毒素性休克（endotoxic shock,ES）过程中血清及肺脏细胞因子的变化,探讨p38比裂素活化蛋白激酶（p38 mito-gen-activated protein kinase,p38 MAPK）的信号转导作用。用生理多道记录仪观察尾静脉注入LPS(p38 mito-gen-activated protein kinase,p38 MAPK）的信号转导作用。用生理多道记录仪观察尾静脉注入 LPS（8mg/kg i.v.）复制的SD大鼠ES模型、LPS注入前10min尾静脉注入CCK-8(40ug/kg i.v.）、单独注入CCK-8(40Uug/kg i.v.）或生理盐水（对照）的四组大鼠平均动脉血压（MAP）的改变,应用ELISA试剂盒检测血清和肺脏中炎性细胞因子（TNF-a、IL-1β和IL-6）的变化。用Western blot检测肺脏p38 MAPK的表达。结果显示：CCK-8可改善LPS引起的大鼠MAP的下降。与对照组相比,LPS可显著增加血清和肺脏TNF-a、IL-1β和IL-6含量;CCK-8可显著抑制LPS诱导的血清和肺脏TNF-a、IL-1β和IL-6的增加。CCK-8可增加ES大鼠肺脏磷酸化p38 MAPK的表达。结果提示CCK-8可改善ES大鼠MAP的降低,并对肺脏促炎性细胞因子过量产生有抑制作用,p38MAPK可能参与了其信号转导机制。

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.