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切莱科克西布和罗费科克西布对小肠缺血/反损伤对大鼠有不同的影响
Szilvia B László1, Barbara Hutka1,2, András S Tóth1,3
1Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Frontiers in pharmacology
|November 25, 2024
概括
选择性COX-2抑制剂如赛莱科西布在肠道缺血/再输 (I/R) 损伤中表现出抗炎作用,但不能防止粘膜损伤. 这些药物对I / R诱导的肠道损伤具有有限的治疗价值.
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.
- 炎症研究 炎症研究
背景情况:
- 肠道缺血/再输 (I/R) 损伤存在严重的死亡风险,治疗选择有限.
- 循环氧基因酶-2 (COX-2) 表达提高了后介质I / R,促使对选择性COX-2抑制剂进行治疗的研究.
- 选择性COX-2抑制剂在减轻I/R诱导的肠道损伤方面的有效性仍在争论中.
研究的目的:
- 为了比较selecoxib和rofecoxib选择性COX-2抑制剂对大鼠实验诱导肠道I/R损伤的治疗效果.
- 评估这些抑制剂对炎症媒介,紧结蛋白和组织学损伤的影响.
- 评估对已知的COX抑制剂异位和亡标记物的影响.
主要方法:
- 威斯塔尔大鼠在假装手术或中肠内肠注射前8天接受了赛莱科克西布 (10,100毫克/公斤) 或罗费科克西布 (5,50毫克/公斤) 或载体.
- 肠道炎症和组织损伤通过组织学和蛋白质定量评估.
- 分析了COX酶活性,炎症调解剂,紧结蛋白和亡标记物.
主要成果:
- 高剂量的赛莱科克西布减少了炎症调解剂 (MPO,PTX3,COX-2,IL-1β) 和紧结蛋白损失,但没有预防粘膜损伤.
- 罗菲科西布在测试剂量时没有显著的抗炎或保护作用.
- 塞莱科克西布增加了Bax/Bcl-2比率 (亡标志物),而罗菲科克西布减少了-Akt;既没有影响HO-1或PPAR-γ.
- 高剂量的赛莱科克西布抑制了肠道的COX-1活性,与罗菲科克西布不同.
结论:
- 切莱科克西布在介质体I / R损伤中显示出比罗菲科克西布更大的抗炎疗效,可能是由于COX-2选择性较低.
- 尽管具有抗炎作用,但高剂量的赛莱科克西布未能减轻粘膜的整体损伤.
- 选择性COX-2抑制剂在治疗肠道I/R损伤方面具有有限的治疗潜力.
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