理中汤调控Raf/MEK/ERK信号通路抗大鼠胃溃疡的效应与机制  

Effect of Li-Zhong-Tang on gastric ulcer in rats based on Raf/MEK/ERK signaling pathway and its mechanism

作　　者：宋厚盼[1,2,3] 陈小娟 曾梅艳 陈新怡 仇婧玥 吴嫚婷 彭清华[3] SONG Hou-pan;CHEN Xiao-juan;ZENG Mei-yan;CHEN Xin-yi;QIU Jing-yue;WU Man-ting;PENG Qing-hua(Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine;Key Laboratory of TCM Heart and Lung Syndrome Differentiation&Medicated Diet and Dietotherapy;Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Eye,Ear,Nose and Throat Diseases;Hunan Provincial Key Laboratory of Translational Research in TCM Prescriptions and Zheng,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学中医诊断学湖南省重点实验室 [2]湖南中医药大学中医心肺病证辨证与药膳食疗重点研究室 [3]湖南中医药大学中医药防治眼耳鼻咽喉疾病湖南省重点实验室 [4]湖南中医药大学中医方证研究转化医学湖南省重点实验室,湖南长沙410208

出　　处：《中国药理学通报》2021年第9期1291-1298,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81703920);中国博士后科学基金面上项目(No 2019M662790);湖南省自然科学基金项目(No 2019JJ50442);湖南省教育厅科学研究项目(No 19C1426);湖南中医药大学校级科研基金项目(2020XJJJ012)。

摘　　要：目的基于Raf/MEK/ERK信号通路探究理中汤(LZT)治疗大鼠胃溃疡(GU)的效应及分子机制。方法将SD大鼠随机分为正常组、模型组、埃索美拉唑组、LZT低、高剂量组。肉眼结合HE染色观察胃黏膜溃疡形态改变;测定胃酸和胃蛋白酶活性;ELISA法检测胃黏膜前列腺素E 2(PGE 2)、肿瘤坏死因子α(TNF-α)及超氧化物歧化酶(SOD)含量;免疫荧光法检测胃黏膜p-Raf、p-MEK、p-ERK蛋白表达。结果与正常组比较,模型组大鼠胃黏膜可见明显的溃疡损伤,LZT具有较好的修复大鼠胃溃疡的作用。与模型组相比,LZT治疗组溃疡指数明显降低,胃酸酸度和胃蛋白活性均明显下降,胃黏膜TNF-α含量明显降低、PGE 2含量和SOD活性均明显升高,胃黏膜p-Raf、p-MEK、p-ERK蛋白表达均明显下调。结论理中汤具有良好的治疗大鼠脾胃虚寒型GU的效应,其作用机制可能与干预Raf/MEK/ERK信号通路,调控胃黏膜炎性介质释放和抗氧化作用有关。Aim To investigate the effect of Li-Zhong-Tang(LZT)in the treatment of gastric ulcer(GU)with pattern of spleen-stomach vacuity cold in rats based on Raf/MEK/ERK signaling pathway and the underlying molecular mechanism.Methods SD rats were randomly divided into normal group,GU model group,esomeprazole(ESO)group,LZT low dose and high dose groups.The morphological changes of gastric mucosa were observed by naked eyes and HE staining.The activities of gastric acid and pepsin were measured.The contents of prostaglandin E 2(PGE 2),tumor necrosis factorα(TNF-α),and superoxide dismutase(SOD)in gastrointestinal mucosa were detected by ELISA.The expressions of p-Raf,p-MEK,and p-ERK protein in gastric mucosa were determined by immunofluorescence.Results Compared with normal group,the gastric mucosa of the rats in model group had obvious ulcer damage,and LZT showed a good effect in repairing gastric ulcer in rats.After treatment with LZT,the gastric mucosal ulcerative lesions in rats were significantly repaired.Compared with model group,the ulcer index of the LZT treatment group was significantly reduced,gastric acidity and gastric protein activity were significantly reduced,the content of TNF-αin the gastric mucosa was significantly reduced,PGE 2 content and SOD activity significantly increased,and p-Raf,p-MEK,and p-ERK protein expression in gastric mucosa were significantly down-regulated.Conclusions LZT has a good therapeutic effect on GU with pattern of spleen-stomach vacuity cold in rats.Its mechanism may be related to the intervention of Raf/MEK/ERK signaling pathway,the regulation of the release of inflammatory mediators in gastric mucosa,and the antioxidant effect.

关 键 词：理中汤 脾胃虚寒证 胃溃疡 胃酸 胃蛋白酶 炎性介质 信号通路 

分 类 号：R-332[医药卫生] R256.39