Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Departamento de Medicina, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Braz J Med Biol Res. 2023 Oct 27;56:e12946. doi: 10.1590/1414-431X2023e12946. eCollection 2023.
The role of cyclooxygenase (COXs) isoforms in maintaining colonic mucosal integrity is not fully understood. This study aimed to evaluate the role of COX-1 and -2 on colonic mucosal integrity in an experimental colitis model. Colitis was induced in Wistar rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (20 mg + 50% ethanol). The control group (sham group) received saline only. After 7, 14, or 28 days, colonic samples were removed, and macroscopic lesion scores, wet weight, myeloperoxidase activity, and transepithelial electrical resistance (TER) were determined. In other rat groups, colonic samples from the sham group and a 7th day post-colitis group were mounted in Üssing chambers with the luminal side exposed to a buffer solution (control), acetylsalicylic acid (ASA), SC-560 (COX-1 inhibitor), or celecoxib (COX-2 inhibitor). TER and epithelial permeability to fluorescein were measured. The 7th day colitis group had higher macroscopic damage scores, wet weight, and myeloperoxidase activity and lower basal TER than the sham, 14th day colitis, and 28th day colitis groups. Inhibition of COX-1 but not COX-2 significantly decreased TER and increased permeability to fluorescein in the 7th day post-colitis group compared to the sham group. Additionally, ASA decreased the colonic mucosal integrity on day seven post-colitis compared to the sham group. A decrease in the colonic mucosa integrity in the experimental colitis model can be aggravated only by the inhibition of COX-1, which demonstrated the importance of this enzyme in the maintenance of colonic mucosal integrity.
环氧化酶(COXs)同工型在维持结肠黏膜完整性中的作用尚不完全清楚。本研究旨在评估 COX-1 和 -2 在实验性结肠炎模型中对结肠黏膜完整性的作用。通过向大鼠结肠内给予 2,4,6-三硝基苯磺酸(20mg+50%乙醇)诱导结肠炎。对照组(假手术组)仅给予生理盐水。在第 7、14 或 28 天,取出结肠样本,测定大体病变评分、湿重、髓过氧化物酶活性和跨上皮电阻(TER)。在其他大鼠组中,将假手术组和结肠炎后第 7 天组的结肠样本置于 Ussing 室中,腔侧暴露于缓冲液(对照)、乙酰水杨酸(ASA)、SC-560(COX-1 抑制剂)或塞来昔布(COX-2 抑制剂)中。测定 TER 和上皮对荧光素的通透性。第 7 天结肠炎组的大体损伤评分、湿重、髓过氧化物酶活性均高于假手术组、第 14 天结肠炎组和第 28 天结肠炎组,基础 TER 低于后三组。与假手术组相比,COX-1 抑制剂而非 COX-2 抑制剂可显著降低第 7 天结肠炎组的 TER 并增加荧光素通透性。此外,ASA 可降低第 7 天结肠炎组的结肠黏膜完整性,与假手术组相比。在实验性结肠炎模型中,结肠黏膜完整性的下降仅可通过 COX-1 的抑制来加重,这表明该酶在维持结肠黏膜完整性中的重要性。