益生菌改善尿毒症大鼠肠道巨噬细胞介导的细菌移位  

Probiotics improve intestinal macrophage-mediated bacterial translocation in experimental uremia

作　　者：孙凌霜[1] 刘华[1] 梁珊珊[1] 薛瑾虹 魏萌[1] 蒋红利[1] SUN Lingshuang;LIU Hiia;LIANG Shanshan;XUE Jinghong;WEI Meng;JIANG Hongli(Dialysis Department of Nephrology Hospital,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an ,China)

机构地区：[1]西安交通大学第一附属医院肾脏病医院血液净化科,西安710061

出　　处：《肾脏病与透析肾移植杂志》2019年第1期30-35,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家自然科学基金(81370838)

摘　　要：目的:评估尿毒症大鼠是否存在肠道屏障功能异常及细菌移位,以及益生菌对肠道屏障功能和巨噬细胞功能的保护作用。方法:5/6肾切除造模尿毒症大鼠,随机分为尿毒症组和尿毒症+益生菌组(乳酸杆菌灌胃4周),处死前2h绿色荧光蛋白标记的示踪大肠杆菌灌胃。比较示踪菌移位情况、肠道黏膜屏障功能、肠道通透性、血中内毒素和炎症因子水平。透射电子显微镜观察肠巨噬细胞形态;检测肠组织中早期生长因子1(EGR1)以及Toll样受体4(TLR4) mRNA和蛋白的表达。结果:尿毒症组肠道组织、肠系膜淋巴结、肝脏、脾脏中可见绿色荧光标记的示踪菌并且示踪菌与巨噬细胞共定位。服用益生菌后,示踪菌在肠道和肠系膜淋巴结、肝脏、脾脏中的数量较服用前减少;肠道黏膜上皮细胞排列整齐、微绒毛结构完整、紧密连接结构模糊程度减轻;肠道通透性下降(P<0.05);血中内毒素、C反应蛋白(CRP)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)(均P<0.05)水平显著降低;肠巨噬细胞伪足和突触增多;EGR1及TLR4 mRNA和蛋白的表达较前明显减少。结论:尿毒症状态下,肠道细菌发生移位,巨噬细胞起到载体的作用,存在巨噬细胞吞噬功能障碍;乳酸杆菌改善细菌移位和微炎症状态。Objective:To investigated the involvement of macrophages in bacterial translocation(BT) and microinflammation in uremic rats and whether Lactobacillus(LB) can influence macrophage activity. Methodology:Macrophages and GFP-labeled tracer bacteria in intestinal and parenteral tissues were observed by fluorescence microscopy. To detect changes after adminstration of LB in the level of intestinal permeability,blood endotoxin,hs-CRP,IL-6,TNF-α. RT-PCR and western blot were employed to assess the mRNA and protein expression of EGR1 and TLR4. Results:In uremic rats,the colocalization of GFP-labeled tracer bacteria and macrophages was visible in intestinal and parenteral tissues. Administration of Lactobacillus LB restored the protrusions and pseudopodia. Compared with the uremia group,the uremia+probiotic group exhibited macrophages with lower mRNA and protein expression of TLR4 and EGR1(P<0.05) and endotoxin,intestinal permeability,hs-CRP,IL-6 and TNF-α were significantly lower than those in uremia group(P<0.05). Conclusion:Macrophages with impaired phagocytic function are associated with BT.

关 键 词：巨噬细胞 细菌移位 微炎症 尿毒症 

分 类 号：R692.5[医药卫生—泌尿科学]