CCK-8对内毒素休克大鼠肺脏细胞因子的抑制效应

Inhibitory effect of cholecystokinin-octapeptide on production of cytokines in the lung of endotoxic shock rats

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 (endotoxicshock ,ES)过程中血清及肺脏细胞因子的变化 ,探讨p38丝裂素活化蛋白激酶 (p38mitogen acti vatedproteinkinase ,p38MAPK)的信号转导作用。用生理多道记录仪观察尾静脉注入LPS (8mg/kgi v )复制的SD大鼠ES模型、LPS注入前 10min尾静脉注入CCK 8(40 μg/kgi v )、单独注入CCK 8(40 μg/kgi 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 α、IL 1β和IL 6 )的变化。用Westernblot检测肺脏p38MAPK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 α、IL 1β和IL 6含量 ;CCK 8可显著抑制LPS诱导的血清和肺脏TNF α、IL 1β和IL 6的增加。CCK 8可增加ES大鼠肺脏磷酸化p38MAPK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 。

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 μg/kg i v ) pretreatment 10 min before LPS (8 mg/kg) administration, group of CCK 8 (40 μg/kg i v ) only , and normal saline (control) group; the contents of proinflammatory cytokines (TNF α, IL 1β 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 α, IL 1β and IL 6 in serum and lung significantly, while CCK 8 significantly inhibited the LPS induced increases in TNF α, IL 1β 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.