同时抑制COX-1和COX-2不足以诱导与慢性NSAID使用相关的肠病
非类固醇抗炎药物 (NSAIDs) 引起胃肠道问题主要不是由于抑制前列腺素. 肠道微生物组的变化,或失生症,放大NSAID肠道病变,如在小鼠模型和人类数据中所见.
科学领域:
- 胃肠病学 胃肠病学
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 非类固醇抗炎药物 (NSAIDs) 广泛用于慢性疼痛,但会导致严重的胃肠道 (GI) 副作用.
- 传统上,NSAID诱导的肠病症归因于循环氧化酶 (COX) 抑制和随后的前列腺素抑制.
研究的目的:
- 调查NSAID诱导肠道病变背后的主要机制.
- 确定肠道微生物组失调在NSAID肠道病变中的作用.
主要方法:
- 产生了缺乏Cox-1和Cox-2基因的双淘汰赛小鼠.
- 给出的NSAID (纳普罗森) 和非COX抑制剂类似于淘汰和控制小鼠.
- 分析了肠道微生物组合和肠道出血的发生率.
- 与人类队列中的肠道出血相关的NSAID和抗生素的同时使用 (英国生物银行,我们所有人).
主要成果:
- 如果没有NSAID治疗,Cox-1和Cox-2单独的产后删除不会诱导肠道损伤.
- 对考克斯缺陷小鼠的NSAID治疗导致肠道病变,而非COX抑制剂也会诱导损伤.
- 考克斯删除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.
- 在Cox缺陷小鼠中,共同住宿延迟了NSAID诱导的胃肠道出血.
- 人类数据显示,NSAID和抗生素的同时使用与增加的胃肠道出血有关.
结论:
- 抑制前列腺素在NSAID引起的肠道病变中起到很小的作用.
- 由Cox删除诱导的肠道微生物组失调,显著放大了对NSAIDs的肠道性反应.
- 这些发现凸显了肠道微生物群在NSAID相关的肠道毒性中的关键作用.
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