Morris G P, Fallone C A, Pringle G C, MacNaughton W K
Department of Biology, Queen's University, Kingston, Ontario, Canada.
J Clin Gastroenterol. 1998;27 Suppl 1:S53-63. doi: 10.1097/00004836-199800001-00010.
We tested the hypothesis that rapidly developing gastric cytoprotection produced by topical application of exogenous compounds is a result of increased gastric mucosal fluid secretion. Ex vivo gastric chambers were prepared in rats which were subsequently exposed topically to one of the prostaglandin (PG) E1 analogues misoprostol or rioprostil, PGE2, nicotine, N-ethylmaleimide (NEM), 0.25 M HCl, or to their respective vehicles. All agents were added to empty chambers to avoid complications resulting from dilution by gastric contents. Effects of these agents on intraluminal volume changes, blood flow, juxtamucosal pH, histology, and on the mucosal damage resulting from necrotizing agents were studied. All six agents were cytoprotective and each increased net secretion of fluid by the chambered mucosae. Gastric blood flow was not significantly increased by NEM, by 0.25 M HCl, or by nicotine compared to controls, and the juxtamucosal pH was not significantly increased by any of the three agents for which this was studied. Vacuole formation in surface epithelial cells and subepithelial edema were seen after exposure to some agents, but none of the agents led to formation of a thick barrier of exfoliated cells and mucus. Ablation of primary afferent nerves with capsaicin abolished both protection by 0.25 M HCl and the net increase in fluid secretion by the mucosae. Capsaicin ablation did not alter either the protection afforded by NEM or the increase in volume of secretion. We conclude that increased mucosal fluid secretion is the common factor present with all six cytoprotective agents and hence may be the predominant mechanism of cytoprotection against topically applied necrotizing agents.
我们验证了这样一个假设，即局部应用外源性化合物产生的快速发展的胃细胞保护作用是胃黏膜液体分泌增加的结果。在大鼠中制备离体胃腔，随后将其局部暴露于前列腺素（PG）E1类似物米索前列醇或利奥前列素、PGE2、尼古丁、N - 乙基马来酰亚胺（NEM）、0.25 M盐酸或它们各自的赋形剂中。所有试剂均添加到空的胃腔中，以避免因胃内容物稀释而产生的并发症。研究了这些试剂对腔内体积变化、血流、黏膜下pH值、组织学以及对坏死剂引起的黏膜损伤的影响。所有六种试剂都具有细胞保护作用，并且每种试剂都增加了有腔黏膜的液体净分泌。与对照组相比，NEM、0.25 M盐酸或尼古丁并未使胃血流量显著增加，并且在所研究的三种试剂中，没有一种能使黏膜下pH值显著升高。暴露于某些试剂后可见表面上皮细胞空泡形成和上皮下水肿，但没有一种试剂导致形成由脱落细胞和黏液组成的厚屏障。用辣椒素消除初级传入神经后，0.25 M盐酸的保护作用和黏膜液体分泌的净增加均被消除。辣椒素消除并没有改变NEM提供的保护作用或分泌量的增加。我们得出结论，黏膜液体分泌增加是所有六种细胞保护剂共有的因素，因此可能是针对局部应用坏死剂的细胞保护的主要机制。
