基于Nrf2/ARE信号通路探讨硫氢化钠对溃疡性结肠炎大鼠肠黏膜损伤的影响  

Effects of NaHS on intestinal mucosal injury in ulcerative colitis rats based on Nrf2/ARE signaling pathway

作　　者：陈泰宇[1] 唐学贵[1] 蒋小东 唐诗宇 陈思敏[3] 李敏[1] Tai-yu Chen;Xue-gui Tang;Xiao-dong Jiang;Shi-yu Tang;Si-min Chen;Min Li(Anorectal Department of Integrated Traditional Chinese and Western Medicine Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637001,China;Department of Urology of North Sichuan Medical College,Nanchong,Sichuan 637001,China;North Sichuan Medical College,Nanchong,Sichuan 637100,China)

机构地区：[1]川北医学院附属医院中西医结合肛肠科,四川南充637001 [2]川北医学院附属医院泌尿外科,四川南充637001 [3]川北医学院,四川南充637100

出　　处：《中国现代医学杂志》2022年第19期38-43,共6页China Journal of Modern Medicine

基　　金：国家自然科学基金面上项目(No:82074429);南充市2022年市校科技战略合作专项(No:22SXQT0076)。

摘　　要：目的基于Nrf2/ARE信号通路探讨硫氢化钠对溃疡性结肠炎(UC)大鼠肠黏膜损伤的影响。方法将27只UC大鼠随机分为模型组、阳性对照组及硫氢化钠组,每组9只,另取8只正常大鼠为对照组。阳性对照组大鼠于模型复制成功后第3天给予柳氮磺胺吡啶(SASP)混悬溶液0.5 g/(kg·d)灌胃给药,硫氢化钠组大鼠于同时间腹腔注射1 mL硫氢化钠溶液(100μmol/L,1次/d,连续7 d),模型组和对照组于同时间腹腔注射等量生理盐水,观察大鼠一般情况。酶联免疫吸附试验检测白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平;苏木精-伊红染色观察大鼠结肠组织病理学变化;Western blotting检测大鼠结肠组织中核因子E2相关因子2/抗氧化反应元件(Nrf2/ARE)信号通路蛋白水平的变化。结果与对照组比较,模型组、阳性对照组及硫氢化钠组大鼠血清IL-8水平、TNF-α水平升高(P<0.05);与模型组比较,阳性对照组和硫氢化钠组大鼠血清IL-8水平、TNF-α水平降低(P<0.05)。模型组、阳性对照组及硫氢化钠大鼠结肠黏膜组织CMDI评分比较,差异有统计学意义(P<0.05),阳性对照组和硫氢化钠组大鼠结肠黏膜组织CMDI评分低于模型组(P<0.05)。模型组大鼠结肠黏膜上皮缺损,可见黏膜水肿、充血、溃疡灶,伴有大量炎症细胞浸润;阳性对照组、硫氢化钠组大鼠结肠黏膜上皮部分缺损,腺体排列尚规则,充血、水肿较轻,伴有少量炎症细胞浸润。与对照组比较,模型组、阳性对照组及硫氢化钠组大鼠结肠组织Nrf2、ARE蛋白水平降低(P<0.05);而阳性对照组和硫氢化钠组大鼠结肠组织Nrf2、ARE蛋白水平高于模型组(P<0.05)。结论硫氢化钠能够改善UC大鼠肠黏膜损伤,可能是通过促进Nrf2/ARE信号通路活化进而抑制肠黏膜炎症反应实现的。Objective To investigete the effects of NaHS on intestinal mucosal injury in ulcerative colitis rats based on Nrf2/ARE signaling pathway.Methods Twenty seven rats were randomly divided into model group,sodium hydrogen sulfide group,and positive control group,each group consisted of 9 rats,and 8 normal rats were used as control group.Rats in the Nahs group were intraperitoneally injected with NaHS(1 mL)solution 100μmol/L(once a day for 7 days)3 days after the model was established,the positive control group was given sulfasalazine(SASP)suspension 0.5 g/kg intragastrically at the same time.The control group and the model group were given the same amount of saline intraperitoneally at the same time.The serum levels of IL-8 and TNF-αwere measured by enzyme-linked immunosorbent assay(ELISA),and the changes of Colon histopathology were observed by HE staining.Western blotting was used to detect the changes of Nrf2-related factor 2/antioxidant response element(Nrf2/ARE)in rat colon.Results Compared with the control group,serum IL-8 and TNF-αin model group,positive control group,and sodium hydrosulfide group were higher.Compared with the model group,the levels of IL-8 and TNF-αin serum of rats in positive control group and sodium hydrosulfide group increased(P<0.05).The level and CMDI score of colon tissue in the model group were lower than those in the model group(P<0.05).In the model group,colonic mucosal epithelial defect,mucosal edema,congestion,ulcer focus,and a large number of inflammatory cell infiltration were observed.In the positive control group and sodium hydrosulfide group,the mucosal epithelium of colon tissue was partially defective,the arrangement of glands was still regular,and congestion and edema were mild,accompanied by a small amount of inflammatory cell infiltration.Compared with the control group,the levels of Nrf2 and are protein in colonic tissue of model group,positive control group,and sodium thiohydride group decreased(P<0.05),while the levels of Nrf2 and are protein in colonic tissue of p

关 键 词：溃疡性结肠炎 硫氢化钠 肠黏膜损伤 核因子E2相关因子2/抗氧化反应元件 信号通路 

分 类 号：R574.62[医药卫生—消化系统]