Levi S, Goodlad R A, Lee C Y, Stamp G, Walport M J, Wright N A, Hodgson H J
Department of Medicine, Royal Postgraduate Medical School, London, UK.
Lancet. 1990 Oct 6;336(8719):840-3. doi: 10.1016/0140-6736(90)92341-e.
To find out whether non-steroidial anti-inflammatory drugs (NSAIDs) inhibit the proliferation of mucosal cells that normally leads to healing of gastric ulcers a microdissection technique was used to quantify mitosis in gastric glands at the ulcer edge in relation to that in the adjacent mucosa. The regeneration index thus obtained of the ulcer edge was greater in the 9 subjects with gastric ulcers not taking NSAIDs (mean index 3.1 [SEM 0.61]) than that in the 8 patients taking NSAIDs (index 1.49 [0.16]). In rats in which gastric ulcers were produced with a cryoprobe, the ulcers were larger and slower to heal in those receiving indomethacin than in controls; also, immunohistochemical staining indicated significantly fewer mitotic cells in glands adjacent to the ulcer in indomethacin-treated rats (8 mitoses [SEM 3]) than in control animals (25 [5]). The prostaglandin E1 analogue misoprostol reversed the inhibition of healing and substantially restored the proliferative rate in the animals. Inhibition of epithelial cell division normally involved in gastric ulcer healing would contribute to the high prevalence of gastric ulcer during NSAID therapy.
为了确定非甾体抗炎药（NSAIDs）是否抑制通常会导致胃溃疡愈合的黏膜细胞增殖，采用显微解剖技术对溃疡边缘胃腺中的有丝分裂与相邻黏膜中的有丝分裂进行定量分析。在9例未服用NSAIDs的胃溃疡患者中，由此获得的溃疡边缘再生指数（平均指数3.1[标准误0.61]）高于8例服用NSAIDs的患者（指数1.49[0.16]）。在通过冷冻探头造成胃溃疡的大鼠中，与对照组相比，接受吲哚美辛治疗的大鼠溃疡更大且愈合更慢；此外，免疫组化染色显示，吲哚美辛治疗的大鼠溃疡周边腺体中的有丝分裂细胞明显少于对照动物（8个有丝分裂[标准误3]对25个[5个]）。前列腺素E1类似物米索前列醇可逆转愈合抑制并显著恢复动物的增殖率。抑制通常参与胃溃疡愈合的上皮细胞分裂可能是NSAIDs治疗期间胃溃疡高发的原因。
