EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON LFA-1 AND ICAM-1 EXPRESSION IN GASTRIC-MUCOSA
EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON LFA-1 AND ICAM-1 EXPRESSION IN GASTRIC-MUCOSA
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DOI：
10.1152/ajpgi.1994.266.4.g657
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发表时间：
1994-04-01
影响因子：
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通讯作者：
OBRIEN, PE
中科院分区：
文献类型：
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作者：
ANDREWS, FJ;MALCONTENTIWILSON, C;OBRIEN, PE
白细胞对内皮的粘附似乎在胃损伤中起重要作用。本研究旨在发展免疫组织化学染色技术，研究非甾体抗炎药（NSAIDs）治疗后粘膜中白细胞[淋巴细胞功能相关抗原1 (LFA-1)]和内皮[细胞内粘附分子1 (ICAM-1)]粘附分子的分布和表达顺序。对照组大鼠深部粘膜有803 +/- 72个lfa -1染色细胞/mm(2)，浅表粘膜有134 +/- 32个细胞/mm(2)，全粘膜有6.4 +/- 1.2个icam -1染色血管/mm(2)。灌胃阿司匹林（30 mM; 25.2 +/- 7.2/ mM (2), P < 0.01）和吲哚美辛（20 mg/kg; 20.7 +/- 4.4/ mM (2), P < 0.01）治疗30 min后，粘膜内icam -1染色血管数量明显增加，粘膜损伤明显。米索前列醇（100 μ g/kg）对阿司匹林组（7.6 +/- 1.7/mm(2), P < 0.01）和吲哚美辛组（10.7 +/- 2.6/mm(2), P < 0.05）均有逆转作用。直到NSAID治疗60分钟，lfa -1阳性细胞的数量才显著增加。我们得出结论，在正常胃粘膜中表达粘附分子LFA-1和ICAM-1，并且在非甾体抗炎药治疗后，ICAM-1染色的血管数量迅速增加。ICAM-1表达的增加可能与非甾体抗炎药抑制前列腺素合成有关。这些结果进一步支持了早期血管改变在非甾体抗炎药胃病中的作用。
Leukocyte adhesion to the endothelium appears to play an important role in gastric injury. This study aimed to develop immunohistochemical staining techniques to investigate the distribution and sequence of expression of both leukocyte [lymphocyte function associated antigen 1 (LFA-1)] and endothelial [intracellular adhesion molecule 1 (ICAM-1)] adhesion molecules in the mucosa after treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). In control rats there were 803 +/- 72 LFA-1-stained cells/mm(2) in the deep mucosa, 134 +/- 32 cells/mm(2) in the superficial mucosa, and 6.4 +/- 1.2 ICAM-1-stained blood vessels/mm(2) in the total mucosa. The number of ICAM-1-stained blood vessels in the mucosa increased significantly after 30 min of treatment with intragastric aspirin (30 mM; 25.2 +/- 7.2/mm(2), P < 0.01) and indomethacin (20 mg/kg; 20.7 +/- 4.4/mm(2), P < 0.01) before any appreciable mucosal damage was evident. This increase was reversed by treatment with misoprostol (100 mu g/kg) in both aspirin- (7.6 +/- 1.7/mm(2), P < 0.01) and indomethacin-treated animals (10.7 +/- 2.6/mm(2), P < 0.05). There was no significant increase in LFA-1-positive cells until 60 min of NSAID treatment. We conclude that the adhesion molecules LFA-1 and ICAM-1 are expressed in the normal gastric mucosa and that the number of ICAM-1-stained blood vessels increases rapidly after NSAID treatment. This increase in ICAM-1 expression may be associated with an inhibition of prostaglandin synthesis by NSAIDs. These results provide further support for the role of early vascular changes in NSAID gastropathy.