Porras Monica, Martín Maria Teresa, Yang Ping-Chang, Jury Jennifer, Perdue Mary H, Vergara Patri
Cell Biology, Physiology and Immunology Department, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Inflamm Bowel Dis. 2006 Sep;12(9):843-52. doi: 10.1097/01.mib.0000231571.88806.62.
Although several factors have been implicated in the pathogenesis of inflammatory bowel disease (IBD), the mechanisms underlying the recurrent relapses have not yet been clarified. We hypothesized that epithelial barrier dysfunction, associated with intestinal motor disturbances, could play a key role in exacerbation of inflammatory illness due to an increased uptake of luminal antigen and bacterial translocation.
Indomethacin administration to rats induced a long-lasting oscillation of active and quiescent phases of inflammation associated with phases of hypo and hypermotility. Rats selected at either active or quiescent phase and from 2 to 60 days after indomethacin treatment were used. Short-circuit current; conductance and HRP flux were evaluated in small intestinal segments mounted in Ussing Chambers. Enterocyte endosomes containing HRP and ultrastructural damage were assessed by electron microscopy. Bacterial translocation was determined by cultures from mesenteric lymph nodes.
Rats with induced enteritis in both phases demonstrated a long-lasting increase of epithelial paracellular permeability. In contrast, transcellular permeability was only disturbed during the active phases, coinciding with bacterial translocation and the increase in inflammatory parameters. Furthermore, although mithochondrial damage was observed throughout the inflammatory state, alterations were worse during the active phase.
The sustained enhancement of paracellular permeability could facilitate the constant passage of luminal antigens through the mucosa, and hence, be the basis for chronicity. By contrast, transcellular permeability only increases during the active phases, when hypomotility and bacterial translocation are also present, suggesting this factor may play a critical role in the course of acute relapses in IBD.
尽管多种因素与炎症性肠病（IBD）的发病机制有关，但复发的潜在机制尚未阐明。我们推测，与肠道运动紊乱相关的上皮屏障功能障碍，可能因管腔抗原摄取增加和细菌易位而在炎症性疾病的加重中起关键作用。
给大鼠注射吲哚美辛可诱导炎症的活跃期和静止期长期振荡，伴有低动力和高动力阶段。选用在吲哚美辛治疗后2至60天处于活跃期或静止期的大鼠。在安装于尤斯灌流小室的小肠段中评估短路电流、电导和辣根过氧化物酶（HRP）通量。通过电子显微镜评估含有HRP的肠上皮细胞内体和超微结构损伤。通过肠系膜淋巴结培养确定细菌易位情况。
两个阶段患有诱发性肠炎的大鼠均表现出上皮细胞旁通透性长期增加。相比之下，跨细胞通透性仅在活跃期受到干扰，与细菌易位和炎症参数增加同时出现。此外，尽管在整个炎症状态下均观察到线粒体损伤，但在活跃期变化更严重。
细胞旁通透性的持续增强可促进管腔抗原持续透过黏膜，因此是慢性炎症的基础。相比之下，跨细胞通透性仅在活跃期增加，此时也存在低动力和细菌易位，提示该因素可能在IBD急性复发过程中起关键作用。
