MUC2转录下调对急性坏死性胰腺炎大鼠肠道通透性的影响  

Effect of Down-regulated MUC2 Transcription on Intestinal Permeability in Rats With Acute Necrotizing Pancreatitis

作　　者：徐汇 郑俊媛 范俊杰 黄春兰[1] 曾悦[1] XU Hui;ZHENG Junyuan;FAN Junjie;HUANG Chunlan;ZENG Yue(Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai (201620))

机构地区：[1]上海交通大学附属第一人民医院消化科,201620

出　　处：《胃肠病学》2017年第12期717-722,共6页Chinese Journal of Gastroenterology

基　　金：上海交通大学"医工交叉研究基金"面上项目(YG2015MS29)

摘　　要：背景:急性胰腺炎早期即可出现肠屏障功能障碍,并与疾病进展、预后有密切联系。肠黏液层作为主要肠道物理屏障之一,有助于维持正常肠屏障功能。目的:观察黏蛋白MUC2在急性坏死性胰腺炎(ANP)大鼠肠道中的表达变化,探讨其在ANP肠屏障损伤中的作用。方法:42只雄性Sprague-Dawley大鼠随机分为假手术组(SO组)和ANP组,后者以胰胆管逆行注射3.5%牛磺胆酸钠建立ANP模型。分别于造模后6 h、12 h、24 h获取标本,测定血清淀粉酶和D-乳酸(反映肠道通透性)水平,观察胰腺和结肠组织病理学改变,PAS/AB染色观察结肠黏液层和杯状细胞,real-time PCR检测结肠组织MUC2和促炎细胞因子表达。结果:ANP大鼠模型建立成功。ANP组结肠组织损伤明显;与SO组同时间点相比,ANP组肠道通透性增加,结肠黏液层变薄,含黏液杯状细胞数减少,MUC2mRNA表达下调,肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、干扰素-γ(IFN-γ)mRNA表达上调,差异均有统计学意义(P<0.05)。ANP组MUC2表达与肠道通透性和促炎细胞因子表达呈显著负相关(P<0.05)。结论:ANP大鼠结肠组织MUC2转录显著下调,并与肠道通透性增加和病程早期促炎细胞因子过度表达有关。Acute pancreatitis can induce intestinal barrier dysfunction in its early phase,which is closely related with the progression and prognosis of the disease.Intestinal mucus layer not only serves as a physical barrier between pathogens and epithelium,but also plays a critical role in the maintenance of intestinal barrier function.Aims:To investigate the expression and role of mucin2(MUC2)in injured intestinal barrier in rats with acute necrotizing pancreatitis(ANP).Methods:Forty-two male Sprague-Dawley rats were randomly divided into two groups:the sham operation(SO)group and ANP group,which were induced via a retrograde injection of3.5%sodium taurocholate into biliopancreatic duct.Blood,pancreas and colon samples were obtained6,12and24hours after establishing the ANP model for determination of serum amylase and D-lactate(an indicator of intestinal permeability)and histopathological examination.PAS/AB staining was used to observe the colon mucus layer and goblet cells,and the expressions of MUC2and inflammatory cytokines in colonic tissue were detected by real-time PCR.Results:ANP models were successfully established.In ANP group,obvious colonic injury,increased intestinal permeability,thinner colon mucus layer,reduced mucin-containing goblet cells,down-regulated MUC2mRNA and up-regulated tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interferon-γ(IFN-γ)mRNAs were observed at each time point as compared with those in SO group(P<0.05).Spearman correlation coefficient revealed that MUC2expression was negatively correlated with the intestinal permeability and expression of inflammatory cytokines in ANP group(P<0.05).Conclusions:Transcription of MUC2is significantly down-regulated in colonic tissue of ANP rats,and might be associated with increased intestinal permeability and excessive expression of inflammatory cytokines in early phase of ANP.

关 键 词：胰腺炎 急性坏死性 黏蛋白-2 杯状细胞 肠道通透性 

分 类 号：R576[医药卫生—消化系统]