Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Am J Pathol. 2011 Dec;179(6):2885-93. doi: 10.1016/j.ajpath.2011.08.030. Epub 2011 Oct 8.
Lack of enteral feeding, with or without parenteral nutritional support, is associated with increased intestinal permeability and translocation of bacteria. Such translocation is thought to be important in the high morbidity and mortality rates of patients who receive nothing by mouth. Recently, Paneth cells, important constituents of innate intestinal immunity, were found to be crucial in host protection against invasion of both commensal and pathogenic bacteria. This study investigates the influence of food deprivation on Paneth cell function in a mouse starvation model. Quantitative PCR showed significant decreases in mRNA expression of typical Paneth cell antimicrobials, lysozyme, cryptdin, and RegIIIγ, in ileal tissue after 48 hours of food deprivation. Protein expression levels of lysozyme and RegIIIγ precursor were also significantly diminished, as shown by Western blot analysis and IHC. Late degenerative autophagolysosomes and aberrant Paneth cell granules in starved mice were evident by electron microscopy, Western blot analysis, and quantitative PCR. Furthermore, increased bacterial translocation to mesenteric lymph nodes coincided with Paneth cell abnormalities. The current study demonstrates the occurrence of Paneth cell abnormalities during enteral starvation. Such changes may contribute to loss of epithelial barrier function, causing the apparent bacterial translocation in enteral starvation.
肠内喂养的缺乏，无论是伴有还是不伴有肠外营养支持，都与肠道通透性的增加和细菌易位有关。这种易位被认为是导致经口摄入完全禁食的患者高发病率和高死亡率的重要原因。最近，人们发现潘氏细胞（先天肠道免疫的重要组成部分）在宿主抵抗共生菌和病原菌侵袭方面起着至关重要的作用。本研究在小鼠饥饿模型中调查了食物剥夺对潘氏细胞功能的影响。定量 PCR 显示，在禁食 48 小时后，回肠组织中典型的潘氏细胞抗菌肽、溶菌酶、防御素和 RegIIIγ 的 mRNA 表达显著下降。Western blot 分析和免疫组织化学显示，溶菌酶和 RegIIIγ 前体的蛋白表达水平也显著降低。电镜、Western blot 分析和定量 PCR 显示，饥饿小鼠出现晚期退行性自噬溶酶体和异常的潘氏细胞颗粒。此外，细菌易位到肠系膜淋巴结的增加与潘氏细胞异常同时发生。本研究证明了在肠内饥饿期间潘氏细胞发生异常。这种变化可能导致上皮屏障功能丧失，导致肠内饥饿时明显的细菌易位。
