Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.
Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.
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DOI：
10.1371/journal.pone.0023669
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hale LP
中科院分区：
文献类型：
--
作者：
Hampton DD;Hale LP
许多常用的非类固醇抗炎药(NSAIDs)也会引起胃肠道毒性，包括发展成威胁生命的消化性溃疡。我们报告了肥大细胞缺陷小鼠在暴露于非甾体抗炎药吡罗昔康时，严重消化性溃疡的发生率极高。这种增强的溃疡易感性可以通过重组肥大细胞来逆转。此外，用盐酸苯海拉明治疗的野生型小鼠在暴露于吡罗昔康后也会出现类似的高发病率消化性溃疡。苯海拉明是一种常用的抗组胺药物，可以阻断组胺H1受体。肥大细胞的保护作用不依赖于肿瘤坏死因子、H2受体的阻断或酸的分泌。这些数据表明肥大细胞及其产生的组胺在预防和/或修复吡罗昔康诱导的胃粘膜损伤中起着关键作用。还需要更多的研究来确定这是否代表一种非甾体抗炎药的类别效应，可以利用这种效应来开发新的治疗策略，以限制非甾体抗炎药引起的副作用在人类中的发生率。
Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.
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影响因子：
105.7
作者：
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