帕瑞昔布钠对脓毒症小鼠肠黏膜屏障的保护作用  

Protective effect of parecoxib on intestinal barrier function of septic mice

作　　者：吴友平[1] 杨静[1] 彭捷[1] 郄文斌[1] 屠伟峰[1] 

机构地区：[1]广州军区广州总医院麻醉科,510010

出　　处：《临床麻醉学杂志》2017年第11期1091-1095,共5页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金(81501647);广东省科技计划项目(2014A020212555)

摘　　要：目的研究帕瑞昔布钠对脓毒症小鼠肠黏膜屏障功能的影响及可能机制。方法 21只C57BL/6小鼠随机分为三组:假手术组(Sham组)、脓毒症模型组(CLP组)、脓毒症模型+帕瑞昔布钠2mg/kg治疗组(P组),每组7只。术后24h用襻环结扎法检测各组小鼠小肠通透性。另21只C57BL/6小鼠随机分为三组,分组及治疗同前,术后24h处死小鼠,收集小鼠回肠。小肠组织行HE染色观察肠病理损伤。采用Western bolt法检测小肠ZO-1、Occludin、Claudin-1等紧密连接蛋白的表达。采用ELISA法检测小肠黏膜IL-6、PGE2的浓度。结果与Sham组比较,CLP组小鼠小肠明显损伤,门静脉血内FD4浓度明显升高,小肠黏膜内ZO-1、Occludin、Claudin-1蛋白表达明显减少、IL-6与PGE2浓度明显升高(P<0.05)。与CLP组比较,P组小鼠小肠损伤明显减轻(P<0.05),门静脉血内FD4浓度明显降低(P<0.05),小肠黏膜内各蛋白表达水平明显增加、IL-6与PGE2浓度明显降低(P<0.05)。结论帕瑞昔布钠治疗可以明显降低脓毒症导致的肠黏膜屏障功能损伤,其机制可能与降低肠组织炎症水平,增加肠紧密连接蛋白表达相关。Objective To observe the effect of parecoxib on intestinal barrier function of septic mice.Methods Sepsis was induced by cecal ligation and puncture（CLP）model.Twenty-one male C57 BL/6 mice were randomly divided into three groups（n=7 in each group）：group Sham,group CLP,group P（parecoxib 2 mg/kg was administered via gastric tube 2 hafter CLP）.In vivo intestinal permeability was measured using an in vivo ligated loop model 24 hafter surgery.Twenty-one male C57 BL/6 mice were randomly divided into three groups as before.The small intestine tissue sample was harvested 24 hafter surgery.The intestinal pathological changes were observed under light microscope.The expression of tight junction proteins ZO-1,Occludin,and Claudin-1 in the ileum were measured by Western blot.IL-6 and PGE2 level in the ileum were measured by ELISA.Results Compared with group Sham,the intestinal permeability was significantly increased and there was a significant intestinal pathological injury in group CLP.IL-6 and PGE2 level in the ileum was significantly increased and the expression of tight junction protein ZO-1,Occludin,and Claudin-1 in the ileum were reduced in the group CLP（P〈0.05）.Compared with the group CLP,intestinal permeability and pathological injury was significantly reduced in the group P.The levels of IL-6 and PGE2 were significantly decreased（P〈0.05）,the expression of ZO-1,Occludin,and Claudin-1 were upregulated in group P（P〈0.05）.Conclusion Parecoxib can decrease the levels of proinflammatory factors and up-regulate the expression of tight junction to reverse intestinal barrier dysfunction caused by sepsis in mice.

关 键 词：帕瑞昔布钠 脓毒症 肠黏膜屏障功能 紧密连接蛋白 

分 类 号：R459.7[医药卫生—急诊医学]