Lyons K C, Andrews F J, Comper W D, O'Brien P E
Department of Surgery, Monash University, Alfred Hospital, Prahran, Australia.
Dig Dis Sci. 1997 Aug;42(8):1755-64. doi: 10.1023/a:1018830002964.
The aim of this study was to examine the synthesis of sulfated glycosaminoglycans during normal healing of experimental acetic acid-induced gastric ulcer in rats and to investigate the effect of indomethacin, a drug known to delay ulcer healing, on this synthesis using an in vivo labelling system. Analysis revealed the presence of two major sulfated species in control tissue; a population of sulfated mucins and glycosaminoglycans, predominantly galactosaminoglycans. The incorporation of [35S]sulfate label into glycosaminoglycans synthesized in the granulation tissue of healing ulcers increased significantly (P < 0.05) as compared to day 0 and control levels at day 14. Treatment of animals with indomethacin (1 mg/kg daily) resulted in a further significant (P < 0.01) rise in sulfated glycosaminoglycan synthesis in indomethacin-treated ulcer tissue compared to that found in healing ulcers at day 14. The increased glycosaminoglycan synthesis was due to increased levels of chondroitin sulfate and dermatan sulfate. Glycosaminoglycan synthesis is elevated at the ulcer site during healing of experimental gastric ulcers; however, indomethacin treatment, which delays ulcer healing, significantly increases the synthesis of glycosaminoglycans above that seen in healing ulcers. Changes in the sulfated glycosaminoglycan content of the ulcer may play a role in the healing process and may give further insight into the mechanisms by which indomethacin delays ulcer healing.
本研究的目的是检测大鼠实验性乙酸诱导胃溃疡正常愈合过程中硫酸化糖胺聚糖的合成，并使用体内标记系统研究已知会延迟溃疡愈合的药物吲哚美辛对这种合成的影响。分析显示对照组织中存在两种主要的硫酸化物质；一群硫酸化粘蛋白和糖胺聚糖，主要是半乳糖胺聚糖。与第0天相比，愈合溃疡肉芽组织中合成的糖胺聚糖中[35S]硫酸盐标记的掺入量在第14天显著增加（P < 0.05），并与对照水平相当。用吲哚美辛（每日1 mg/kg）治疗动物导致吲哚美辛治疗的溃疡组织中硫酸化糖胺聚糖合成与第14天愈合溃疡相比进一步显著（P < 0.01）升高。糖胺聚糖合成增加是由于硫酸软骨素和硫酸皮肤素水平升高。在实验性胃溃疡愈合过程中，溃疡部位的糖胺聚糖合成升高；然而，延迟溃疡愈合的吲哚美辛治疗显著增加了糖胺聚糖的合成，高于愈合溃疡中的合成水平。溃疡中硫酸化糖胺聚糖含量的变化可能在愈合过程中起作用，并可能进一步深入了解吲哚美辛延迟溃疡愈合的机制。
