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同时抑制COX-1和COX-2并不足以诱导与慢性NSAID使用相关的肠病
Kayla Barekat1, Soumita Ghosh1, Christin Herrmann2
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America.
非类固醇抗炎药物 (NSAIDs) 不主要通过抑制前列腺素引起胃肠道问题. 相反,NSAID使用与肠道微生物组变化相结合,会放大肠道损伤.
科学领域:
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
- 微生物组研究 微生物组研究
背景情况:
- 非类固醇抗炎药物 (NSAIDs) 广泛用于慢性疼痛,但会引起胃肠道 (GI) 的不良事件.
- 传统上,NSAID诱导的肠病症归因于循环氧化酶 (COX) 抑制和减少前列腺素合成.
研究的目的:
- 调查前列腺素合成抑制与其他机制在NSAID诱导的肠道病变中的作用.
- 探索肠道微生物组改变对NSAID诱导的胃肠道毒性的影响.
主要方法:
- 产生的小鼠产后删除了COX-1和COX-2.
- 给出的NSAID (纳普罗森) 和非COX抑制剂类似于淘汰赛小鼠.
- 分析了肠道微生物组合和共同住房的影响.
- 检查了人类队列 (英国生物银行,我们所有人) 关于NSAID和抗生素使用与肠道出血之间的关联.
主要成果:
- 仅仅COX删除并没有引起肠道损伤;需要NSAID治疗.
- 即使使用非COX抑制剂模拟剂,也观察到NSAID诱导的肠病变.
- 脱离COX导致了明显的肠道微生物组失调,这部分是通过共同住房来挽救的.
- 共同住宿延迟了麻小鼠的NSAID诱导的胃肠道出血.
- 人类数据显示,在同时服用抗生素和NSAID时,胃肠道出血风险增加.
结论:
- 抑制前列腺素在NSAID诱导的肠道病变中起到较小的作用.
- 由COX删除引起的肠道微生物组失调会放大NSAID肠道病变.
- 肠道微生物组是NSAID诱导的胃肠道毒性的关键因素.
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