p38MAPK参与胰蛋白酶诱导的食管上皮细胞炎症  

The mechanism of p38 MAPK action in trypsin-induced inflammatory reaction of esophageal mucosal epithelial cells

作　　者：柳刚[1] 张玲[1] 郭晓军[2] 李桂香[1] 邹多武[1] 

机构地区：[1]第二军医大学附属长海医院消化内科,上海200433 [2]济南军区青岛第二疗养院干部二科

出　　处：《中国医师杂志》2015年第5期671-674,共4页Journal of Chinese Physician

基　　金：国家自然基金青年科学基金资助项目（81200273）

摘　　要：目的 研究p38 MAPK在胰蛋白酶（trypsin）诱导食管黏膜上皮细胞炎症反应中的机制.方法 原代培养食管黏膜上皮细胞,使用胰蛋白酶进行刺激,观察p38 MAPK磷酸化程度;给予p38 MAPK抑制剂SB203580（1、10 μmol/L）进行干预治疗,观察炎症相关指标的变化.结果 胰蛋白酶刺激剂量依赖地增加了p38 MAPK磷酸化,提示胰蛋白酶激活了食管黏膜上皮细胞中的p38MAPK通路;SB203580治疗抑制了胰蛋白酶诱导的炎症因子白介素8（IL-8）、环氧酶2（COX2）、肿瘤坏死因子α（TNFα）的mRNA表达水平,同时抑制了胰蛋白酶诱导的食管上皮细胞中诱导性一氧化氮合酶（iNOS）的蛋白表达和细胞中一氧化氮（NO）的生成.结论 p38 MAPK通过调节IL-8、COX2、TNFα、iNOS等炎症相关因子参与了胰蛋白酶诱导的食管黏膜上皮损伤.Objective To investigate the role of p38 MAPK in the trypsin-induced injury in human esophageal epithelial cells.Methods Primary cultured human esophageal epithelial cells were stimulated with trypsin （20,40,and 80 μg/ml） for4 hours,phosphorylation of p38 MAPK was evaluated by Western blotting.Primary cultured human esophageal epithelial cells were stimulated with trypsin （40 μg/ml） and treated with p38 MAPK inhibitor （SB203580,1 and 10 μmol/L） simultaneously.Four hours later,the cells were collected for analysis.Results Western blotting results revealed that stimulation with trypsin enhanced phosphorylation of p38 MAPK,indicating that trypsin activated p38 MAPK in esophageal epithelial cells.SB203580 treatment suppressed trypsin-induced expression of pro-inflammatory cytokines including interleukin-8 （IL-8）,cyclooxygenase 2 （COX2）,and tumor necrosis factor alpha （TNFcα）.Finally,SB203580 treatment suppressed trypsin-induced upregulation of protein expression of inducible nitric oxide synthase （iNOS）,and subsequently reduced nitric oxide （NO） levels.Conclusions The regulation of p38 MAPK was involved in the trypsin-induced injury in esophageal epithelial cells.

关 键 词：p38丝裂原活化蛋白激酶类/拮抗剂和抑制剂/药理学/生物合成 胰蛋白酶/副作用 食管/病理学/代谢/药物作用 黏膜/病理学/代谢/药物作用 

分 类 号：R571[医药卫生—消化系统]