复合益生菌制剂对急性坏死性胰腺炎大鼠的保护作用

摘要

背景:肠道细菌易位是重症急性胰腺炎(SAP)时胰腺坏死感染的主要来源,因此保护肠黏膜屏障对SAP的治疗具有重要意义.目的:探讨复合益生菌制剂对急性坏死性胰腺炎(ANP)大鼠肠黏膜屏障和胰腺损伤的保护作用.方法:50只SPF级大鼠随机分为假手术组(n=10)、ANP模型组(n=20)和益生菌干预组(n=20).采用胰腺被膜下均匀注射牛磺胆酸钠制备ANP模型,干预组术前30 min以双歧杆菌四联活菌片溶液灌胃.术后6h采集标本,检测血淀粉酶、二胺氧化酶(DAO)、TNF-α水平,观察胰腺组织病理学表现和末端回肠组织超微结构.结果:ANP模型组血淀粉酶、DAO、TNF-α水平和胰腺组织学评分均显著高于假手术组(P＜0.05),益生菌干预组各项指标均较ANP模型组有所改善(P＜0.05).假手术组末端回肠黏膜结构完整；ANP模型组回肠黏膜上皮细胞微绒毛萎缩、排列稀疏,细胞间连接松弛；益生菌干预组微绒毛稍稀疏,细胞间连接紧密度较ANP模型组增高.结论:复合益生菌制剂对ANP大鼠具有保护作用,不仅能减轻肠黏膜损伤,保护肠黏膜屏障功能,还能减轻胰腺局部损伤和全身性炎症反应.%Background:Bacterial translocation accounts for most infections of pancreatic necrosis in severe acute pancreatitis (SAP),thus protecting against intestinal barrier dysfunction is of great importance for the management of SAP.Aims:To investigate the protective effect of combined probiotics on intestinal barrier and pancreatic injury in rats with acute necrotizing pancreatitis (ANP).Methods:Fifty SPF rats were randomly divided into three groups:sham operated group (n =10),ANP model group (n =20) and probiotics intervention group (n =20).ANP model was induced by injection of sodium taurocholate under the pancreatic membrane.In intervention group,live combined bifidobacterium tablets were administered intragastrically 30 minutes before model construction.Blood,pancreatic and terminal ileal samples were obtained 6 hours after model construction for measurements of serum amylase,plasma diamine oxidase (DAO) and serum TNF-α,as well as observation of pancreatic histopathology and ileal ultrastructure.Results:Serum amylase,plasma DAO,serum TNF-α and histological score of pancreatic tissue were significantly higher in ANP model group than in sham operated group (P ＜ 0.05),and all these parameters were significantly improved in probiotics intervention group than in ANP model group (P ＜ 0.05).Under electron microscopy,sham operated group showed intact mucosal barrier in terminal ileum ;while in ANP model group,the ileal epithelial microvilli were atrophic and sparsely arranged,and the intercellular connections were loosened; in probiotics intervention group slightly sparse microvilli and tightened intercellular connections were seen.Conclusions:Combined probiotics can ameliorate not only intestinal injury and barrier dysfunction but also pancreatic injury and systemic inflammation,which results in a protective effect on ANP rats.