OBJECTIVE: We used an experimental model of high thoracic SCI to investigate (1) regional mucosal oxidative stress using dihydroethidium labeling; (2) regional paracellular permeability to small- and large-molecular probes via Ussing chamber; (3) regional intestinal tight junction (TJ) protein expression; and (4) hindgut perfusion via the caudal mesenteric artery.
RESULTS: Dihydroethidium staining was significantly elevated within duodenal mucosa at 3-day post-SCI. Molar flux of [14C]-urea was significantly elevated in duodenum and proximal colon at 3-day post-SCI, while molar flux of [3H]-inulin was significantly elevated only in duodenum at 3-day post-SCI. Barrier permeability was mirrored by a significant increase in the expression of pore-forming TJ protein claudin-2 in duodenum and proximal colon at 3-day post-SCI. Claudin-2 expression remained significantly elevated in proximal colon at 3-week post-SCI. Expression of the barrier-forming TJ protein occludin was significantly reduced in duodenum at 3-day post-SCI. Caudal mesenteric artery flow was unchanged by SCI at 3 days or 3 weeks despite significant reductions in mean arterial pressure.
CONCLUSIONS: These data show that T3-SCI provokes elevated mucosal oxidative stress, altered expression of TJ proteins, and elevated intestinal barrier permeability in the proximal intestine. In contrast, mucosal oxidative stress and intestinal barrier permeability were unchanged in the hindgut after SCI. This regional heterogeneity may result from differential sensitivity to reduced mesenteric perfusion, though further studies are required to establish a causal link. Understanding regional differences in intestinal pathophysiology is essential for developing effective treatments and standards of care for individuals with SCI.
目的:我们使用高胸椎SCI的实验模型来研究(1)使用二氢乙啶标记的局部粘膜氧化应激;(2)通过Ussing室对小分子和大分子探针的局部细胞旁通透性;(3)局部肠紧密连接(TJ)蛋白表达;(4通过肠系膜尾动脉的后)肠灌注。
结果:在SCI后3天,十二指肠粘膜内二氢乙啶染色显著升高。SCI后3天,[14C]-尿素的摩尔通量在十二指肠和近端结肠中显着升高,而[3H]-菊粉的摩尔通量仅在SCI后3天在十二指肠中显着升高。SCI后3天,十二指肠和近端结肠中成孔TJ蛋白claudin-2的表达显着增加反映了屏障通透性。在SCI后3周时,近端结肠中Claudin-2的表达仍然显着升高。SCI后3天,十二指肠中屏障形成TJ蛋白闭塞蛋白的表达显着降低。尽管平均动脉压显着降低,但SCI在3天或3周时肠系膜尾动脉血流没有变化。
结论:这些数据表明T3-SCI引起粘膜氧化应激升高,TJ蛋白表达改变,和近端肠道的肠屏障通透性升高。相比之下,SCI后后肠粘膜氧化应激和肠屏障通透性无变化。这种区域异质性可能是由于对肠系膜灌注减少的敏感性不同所致。尽管需要进一步的研究来建立因果关系。了解肠道病理生理学的区域差异对于为SCI患者开发有效的治疗方法和护理标准至关重要。