胃肠安丸通过抑制上皮间质化抑制TNBS诱导的大鼠溃疡性结肠炎  

Wei Chang An pill alleviates 2,4,6-trinitro-benzenesulfonic acid-induced ulcerative colitis by inhibiting epithelial-mesenchymal transition process

作　　者：齐雅馨 王梦[2,3] 柴丽娟 张敏[1,2,3] 贾思童 纳塔鹏威蔡 王琳[5] 王玉晶[5] 宋霁翔 张晗 王怡 张鹏 苗琳 Yaxin Qi;Meng Wang;Lijuan Chai;Min Zhang;Sitong Jia;Nuttapong Wichai;Lin Wang;Yujing Wang;Jixiang Song;Han Zhang;Yi Wang;Peng Zhang;Lin Miao(State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,China;Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin;Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae,Ministry of Education,Tianjin University of Traditional Chinese Medicine,Tianjin,China;Faculty of Pharmacy,Mahasarakham University,Kantharawichai,Maha Sarakham Province,Thailand;Tianjin Zhongxin Pharmaceutical Group Co.,Ltd.Le Ren Tang Pharmaceutical Factory,Tianjin,China)

机构地区：[1]天津中医药大学中医药研究院组分中药国家重点实验室,天津 [2]天津中医药大学,中医药学院中医药研究所,天津 [3]天津大学中医药,中药药理学重点实验室教育部医学配方,天津 [4]玛哈萨拉堪大学,药剂学院,泰国 [5]天津中新药业集团有限公司,天津,301617

出　　处：《Acupuncture and Herbal Medicine》2023年第2期107-115,共9页针灸和草药（英文）

基　　金：supported by the Science and Technology Project of Tianjin(22ZXGBSY00020 and 21ZYJFJC0070;National Key Research and Development Project of China(2021YFC1712904);the National Natural Science Foundation of China(82074105).

摘　　要：[目的]探讨胃肠安丸对大鼠溃疡性结肠炎(UC)的抑制作用及其作用机制。[方法]建立2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠UC模型,灌胃给予胃肠安(WCA)1周;记录大鼠体重和结肠长度,进行疾病活动指数(DAI)评分和结肠黏膜损伤指数(CMDI)评分;用免疫组织化学法检测结肠病理变化。细胞水平上,考察WCA对脂多糖(LPS)刺激的THP-1细胞炎症因子表达的影响。通过免疫荧光法分别考察WCA对UC大鼠结肠组织和LPS刺激的THP-1细胞条件培养基(CM)处理的结肠上皮Caco-2细胞的上皮-间质化(EMT)标志物E-钙粘蛋白和波形蛋白的表达。[结果]WCA可以显著抑制UC大鼠体重的减轻和结肠长度的缩短,降低疾病相关的DAI和CMDI评分,改善结肠病理损伤;UC结肠组织髓过氧化物酶(MPO)活性和细胞因子表达的上升已被明显抑制。在THP-1细胞中,WCA及其活性成分可以显著抑制LPS诱导的干扰素诱导蛋白10(IP-10)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和NF-κB抑制剂(IkBα)mRNA水平的表达。在UC大鼠和CM刺激的Caco-2细胞中E-钙粘蛋白表达下调,波形蛋白表达上调,给予WCA治疗处理后,上述EMT现象被明显抑制。[结论]本研究表明,WCA可以通过抑制炎症诱导的结肠EMT减轻大鼠UC的发展。Objective:To investigate the inhibitory effect and mechanism of Wei Chang An pill(WCA)on ulcerative colitis(UC).Methods:A 2,4,6-trinitro-benzenesulfonic acid(TNBS)-induced UC model was established,and WCA was administered orally for 1 week.Body weight,colon length,disease activity index(DAI)score,and colon mucosa damage index(CMDI)score were recorded.Cytokine expression in lipopolysaccharide(LPS)-stimulated THP-1 cells was evaluated to determine the anti-inflammatory effects of WCA and its active ingredients.Immunohistochemistry and immunofluorescence were performed to detect the expression of epithelial-mesenchymal transition(EMT)markers E-cadherin and vimentin in rat UC and WCA groups,and in Caco-2 cells stimulated with conditioned medium(CM)from THP-1 cells,with or without LPS or WCA.Results:WCA significantly inhibited body weight loss,decreased DAI and CMDI scores,blocked colon length shortening,and improved histological damage in UC rats.Furthermore,both myeloperoxidase(MPO)activities and cytokine expression in UC tissues were significantly suppressed by WCA as well.In THP-1 cells,the mRNA expression of interferon-inducible protein(IP)-10,tumor necrosis factor-α(TNF-α),interleukin(IL)-6,and NF-κB inhibitorα(IκBα)was significantly suppressed by WCA and its active ingredients.E-cadherin expression in UC rats and CM-stimulated Caco-2 cells was downregulated and vimentin expression was upregulated,whereas both were blocked when administered with WCA.Conclusions:Our data showed that WCA alleviated UC progression by inhibiting inflammation-induced EMT progression.

关 键 词：上皮间质化 炎症 中药 溃疡性结肠炎 胃肠安 

分 类 号：R285.5[医药卫生—中药学]