Henrikson C K, Argenzio R A, Liacos J A, Khosla J
Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh.
Lab Invest. 1989 Jan;60(1):72-87.
Deoxycholate-induced colonic injury and repair were studied both functionally and morphologically utilizing in vivo loop preparations of the porcine colon. The mucosa was exposed to (a) varying doses (1.5 to 21 mM) of deoxycholate for 30 minutes, (b) 15 mM deoxycholate for varying times and (c) 15 mM deoxycholate for 30 minutes with varying times of recovery. Colonic permeability was assessed by mannitol clearance from blood to lumen and transmural potential difference. After colonic perfusion, tissue samples were collected for light and electron microscopy. Both the degree of mucosal permeability and the amount of superficial epithelial damage increased with increasing concentrations of bile salt culminating in cell necrosis and epithelial sloughing. Denuded colonic surfaces became reepithelialized by migrating, flattened cells in as little as 15 minutes of recovery. Relatively normal appearing columnar epithelium was restituted within 2 hours. Mannitol clearance returned to control values after 30 minutes of recovery, whereas it took potential difference 2 hours of recovery to return to normal. The results of these experiments suggest that (a) the permeability changes measured are most likely due to the lytic action of bile salts which leads to cell degeneration and sloughing of the superficial epithelium, (b) epithelial restitution after superficial damage is remarkably rapid, (c) the formation of a flattened epithelium of immature cells is adequate for restoration of the barrier to macromolecules but ion transport or resistance is slower to recover and (d) repair is due to an active ameboid movement of viable cells out of the crypts onto the surface of the colon.
利用猪结肠的体内肠袢制备方法,从功能和形态学两方面研究了脱氧胆酸盐诱导的结肠损伤及修复过程。将黏膜暴露于:(a) 不同剂量(1.5至21 mM)的脱氧胆酸盐中30分钟;(b) 15 mM脱氧胆酸盐不同时间;(c) 15 mM脱氧胆酸盐30分钟,并恢复不同时间。通过从血液到肠腔的甘露醇清除率和跨壁电位差评估结肠通透性。结肠灌注后,收集组织样本进行光镜和电镜检查。随着胆盐浓度增加,黏膜通透性程度和表面上皮损伤量均增加,最终导致细胞坏死和上皮脱落。裸露的结肠表面在恢复仅15分钟时就被迁移的扁平细胞重新上皮化。在2小时内恢复到相对正常外观的柱状上皮。恢复30分钟后甘露醇清除率恢复到对照值,而电位差则需要2小时恢复到正常。这些实验结果表明:(a) 所测量的通透性变化很可能是由于胆盐的溶解作用导致细胞变性和表面上皮脱落;(b) 表面损伤后的上皮修复非常迅速;(c) 未成熟细胞扁平上皮的形成足以恢复对大分子的屏障,但离子转运或电阻恢复较慢;(d) 修复是由于活细胞从隐窝向结肠表面进行活跃的阿米巴样运动所致。