p38 MAPK和STAT3参与CCK-8抑制LPS诱导的大鼠促炎症细胞因子生成  

Roles of p38 MAPK and STAT3 in inhibitory effect of cholecystokinin octapeptide on LPS-induced cytokine production in rats

作　　者：孟爱宏[1] 凌亦凌[2] 张霄鹏[3] 

机构地区：[1]河北医科大学第二医院呼吸科 [2]河北医科大学病理生理教研室 [3]河北省人民医院,河北石家庄050000

出　　处：《中国病理生理杂志》2013年第6期1095-1101,共7页Chinese Journal of Pathophysiology

基　　金：河北省教育厅博士基金资助项目(No.B2003215);河北省自然科学基金资助项目(No.302490)

摘　　要：目的:观察八肽胆囊收缩素(CCK-8)是否改善脂多糖(LPS)引起的大鼠细胞因子的变化,并探讨p38丝裂原活化蛋白激酶(p38 MAPK)和信号转导子及转录激活子3(STAT3)的信号转导作用,以及CCK受体(CCK-R)的作用。方法:4组大鼠尾静脉分别注入生理盐水(对照)、LPS(8 mg/kg)、CCK-8(40μg/kg)和CCK-8(40μg/kg)+LPS(8 mg/kg),酶联免疫吸附法(ELISA)检测血清、肺脏及脾脏中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-6的变化,Western blotting和免疫荧光双标激光共聚焦显微镜检测肺脏和脾脏磷酸化p38MAPK和磷酸化STAT3的表达,RT-PCR检测脾脏CCK-R亚型的mRNA表达。结果:CCK-8可显著抑制LPS诱导的TNF-α、IL-1β和IL-6的增加。CCK-8可增加LPS诱导的大鼠肺脏和脾脏磷酸化p38 MAPK和磷酸化STAT3的表达。LPS有诱导CCK-AR及CCK-BR mRNA表达量增加的作用。结论:CCK-8对LPS刺激的大鼠促炎症细胞因子过量产生有抑制作用,p38 MAPK和STAT3可能参与了其信号转导机制。LPS刺激时,CCK-R受体发生正向调节,CCK-8有可能用于治疗全身性感染及其它的炎症性疾病。AIM： To investigate the roles of p38 mitogen-activated protein kinase （1）38 MAPK）, signal trans- ducer and activator of transcription 3 （STAT3） and cholecystokinin （CCK） receptor （CCK-R） in the inhibitory effect of cholecystokinin octapeptide （CCK-8） on pro-inflammatory cytokine production in lipopolysaccharide （LPS）-stimulated rats. METHODS： SD rats were randomly divided into LPS （8 mg/kg） group, CCK-8 （40 μg/kg） ＋ LPS （8 mg/kg） group, CCK-8 （40 μg/kg） group and control （normal saline） group. The production of pro-inflammatory cytokines tumor necrosis factor α （TNF-α）,interleukin-lβ （IL-Iβ） and IL-6 in the serum, the lung and the spleen were measured by ELISA. Phosphorylation levels of p38 MAPK and STAT3 in the lung and the spleen of the rats were detected by Western blotting and double label immunofluorescence laser confocal microscopy. The mRNA expression of CCK-A receptor （CCK- AR） and CCK-B receptor （CCK-BR） in the spleen was detected by RT-PCR. RESULTS： CCK-8 significantly inhibited the increases in the levels of TNF-α, IL-1β and IL-6 in the lung and the spleen of LPS-stimulated rats, and also increased the levels of phosphorylated p38 MAPK and STAT3 in the lung and the spleen of the rats. CCK-R was up-regulated by LPS stimulation. CONCLUSION： CCK-8 inhibits LPS-stimulated pro-inflammatory cytokine production in the serum, the lung and the spleen through p38 MAPK and STAT3 pathways. CCK-8 may be useful for treating systemic infection and other in- flammatory diseases.

关 键 词：胆囊收缩素 脂多糖类 细胞因子 p38 MAPK 信号转导子及转录激活子3 大鼠 

分 类 号：Q954.6[生物学—动物学] R363[医药卫生—病理学]