Rioux K P, Wallace J L
Intestinal Disease Research Unit, University of Calgary, Alberta, Canada.
Aliment Pharmacol Ther. 1996 Apr;10(2):173-80. doi: 10.1046/j.1365-2036.1996.724116000.x.
By releasing pro-ulcerogenic mediators, mast cells may contribute to the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
To study this, rat and mouse models of NSAID-induced gastric damage were used in which administration of indomethacin causes haemorrhagic injury in the corpus region of the stomach, and the "re-feeding" model in which penetrating antral ulcers are induced in the rat by naproxen. Mast cell degranulation was determined histologically and by measurement of tissue and serum levels of rat mast cell protease-II, a mediator specific to mucosal mast cells. The effects of either increasing or decreasing the number of gastric mucosal mast cells on the susceptibility of the stomach to injury induced by indomethacin were also studied.
Gastric injury induced by indomethacin was not accompanied by significant mast cell degranulation. Moreover, neither increasing nor decreasing the number of gastric mucosal mast cells had a significant effect on the susceptibility of the gastric mucosa to damage induced by indomethacin. In the re-feeding model, prior depletion of gastric mucosal mast cells did not significantly affect the severity of antral ulceration induced by naproxen, nor the ability of prostaglandin E2 to prevent this damage. Finally, indomethacin-induced damage was similar in severity in mice with a genetic defect resulting in the complete absence of mast cells as it was in normal, congenic littermates.
Mast cells do not play a significant role in the development of gastric injury induced by acute NSAID administration in the rat or mouse.
肥大细胞通过释放促溃疡介质，可能参与了与使用非甾体抗炎药（NSAIDs）相关的黏膜损伤。
为研究此问题，使用了NSAID诱导的大鼠和小鼠胃损伤模型，其中给予吲哚美辛会导致胃体部出血性损伤，以及“再喂养”模型，即通过萘普生在大鼠中诱导穿透性胃窦溃疡。通过组织学检查以及测量大鼠肥大细胞蛋白酶-II（一种黏膜肥大细胞特异性介质）的组织和血清水平来确定肥大细胞脱颗粒情况。还研究了增加或减少胃黏膜肥大细胞数量对胃对吲哚美辛诱导损伤易感性的影响。
吲哚美辛诱导的胃损伤并未伴随明显的肥大细胞脱颗粒。此外，增加或减少胃黏膜肥大细胞数量对胃黏膜对吲哚美辛诱导损伤的易感性均无显著影响。在“再喂养”模型中，预先耗尽胃黏膜肥大细胞并未显著影响萘普生诱导的胃窦溃疡严重程度，也未影响前列腺素E2预防这种损伤的能力。最后，吲哚美辛诱导的损伤在因基因缺陷导致完全缺乏肥大细胞的小鼠中的严重程度与正常同基因 littermates 相似。
肥大细胞在大鼠或小鼠急性NSAID给药诱导的胃损伤发展中不发挥重要作用。
