Lipscomb G R, Rees W D
Salford Royal Hospitals NHS Trust, University of Manchester School of Medicine, UK.
Aliment Pharmacol Ther. 1996 Apr;10(2):133-8. doi: 10.1046/j.1365-2036.1996.726118000.x.
Oral nonsteroidal anti-inflammatory drugs (NSAIDs) cause acute gastric mucosal injury but the relative importance of systemic and topical effect of NSAIDs to overall gastric damage remains uncertain.
Twenty-four healthy volunteers were allocated either oral or rectal naproxen 500 mg b.d. and gastroscoped before and during days 1, 7 and 28 of dosing. Macroscopic gastric damage was assessed using a modified Lanza score, mucosal blood flow recorded using laser Doppler flowmetry and prostaglandin E2 (PGE2) measured in antral mucosal biopsies.
Maximal gastric damage occurred during the first 24 h in the oral naproxen group and was associated with a fall in antral mucosal blood flow (mean +/- S.E.M.) from 58.2 +/- 3.3 to 46.6 +/- 4.1 arbitrary units (a.u.) (P < 0.05). With continued administration of oral naproxen, gastric damage resolved and antral mucosal blood flow returned to baseline (54.2 +/- 3.7 a.u.). No macroscopic damage or significant changes in mucosal blood flow were observed during rectal administration. There was no significant difference between mucosal PGE2 concentrations in those receiving oral or rectal naproxen, falling from an initial level of 335 +/- 29 to 155 +/- 49 pg/mg at day 1 (P = 0.06) in those receiving oral naproxen and from 235 +/- 55 to 107 +/- 31 pg/mg at day 1 (P = 0.1) in those receiving rectal naproxen, and remaining suppressed throughout the study in both groups.
These observations suggest that acute mucosal damage and changes in mucosal blood flow are caused by the topical rather than systemic actions of naproxen.
口服非甾体抗炎药（NSAIDs）可导致急性胃黏膜损伤，但NSAIDs的全身作用和局部作用对整体胃损伤的相对重要性仍不确定。
24名健康志愿者被分配口服或直肠给予萘普生500mg，每日两次，并在给药第1、7和28天之前及期间进行胃镜检查。使用改良的兰扎评分评估宏观胃损伤，用激光多普勒血流仪记录黏膜血流量，并在胃窦黏膜活检中测量前列腺素E2（PGE2）。
口服萘普生组在最初24小时内出现最大胃损伤，且与胃窦黏膜血流量（平均值±标准误）从58.2±3.3任意单位（a.u.）降至46.6±4.1 a.u.相关（P<0.05）。随着口服萘普生的持续给药，胃损伤消退，胃窦黏膜血流量恢复至基线水平（54.2±3.7 a.u.）。直肠给药期间未观察到宏观损伤或黏膜血流量的显著变化。接受口服或直肠萘普生者的黏膜PGE2浓度无显著差异，口服萘普生者在第1天从初始水平335±29降至155±49 pg/mg（P = 0.06），直肠萘普生者在第1天从235±55降至107±31 pg/mg（P = 0.1），且两组在整个研究过程中均持续受到抑制。
这些观察结果表明，急性黏膜损伤和黏膜血流量变化是由萘普生的局部作用而非全身作用引起的。
