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Pathophysiological studies of trinitrobenzene sulfonic acid-induced colitis in Syrian hamsters (Mesocricetus auratus)

机译:三硝基苯磺酸诱导的仓鼠结肠炎的病理生理研究(Mesocricetus auratus)

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We developed a colitis model in Syrian hamsters (Mesocricetus auratus) to investigate the relationship between colitis and neutrophil elastase (NE). Colitis was induced by a single intracolonic dose of trinitrobenzene sulfonic acid (TNBS; 90 mg/ml) dissolved in 15% (vol/vol) ethanol. The ulcer area, tissue myeloperoxidase (MPO) activity, and luminal NE activity all were increased on Days 1 and 5, corresponding with the acute inflammatory histopathological changes. These acute inflammatory parameters subsequently decreased by Day 14, and chronic inflammatory histopathological changes became evident. Recurrence of inflammation was not observed during the period up to Day 28. To evaluate our colitis model, the effects of prednisolone were examined. Prednisolone was administered orally once on the day before induction of colitis, and animals were treated twice daily thereafter. Although prednisolone had little effect on the tissue MPO activity, prednisolone inhibited the ulcer area and NE activity. In addition, the effects of an NE-specific inhibitor (ONO-6818) on our TNBS-induced colitis model were examined. In the subcutaneous treatment study, ONO-6818 was administered once before the induction of colitis. Although ONO-6818 had little effect on the tissue MPO activity, the ulcer area and NE activity were decreased in the ONO-6818-treated group. The inhibitory effects on the ulcer area and NE activity were confirmed after oral treatment with ONO-6818 after induction of colitis. We conclude that our colitis model is useful for investigating the relationship between colitis and NE, and inhibition of NE activity can prevent the progression of ulceration.
机译:我们在叙利亚仓鼠(Mesocricetus auratus)中建立了结肠炎模型,以研究结肠炎和中性粒细胞弹性蛋白酶(NE)之间的关系。通过单次结肠内剂量的三硝基苯磺酸(TNBS; 90 mg / ml)溶于15%(vol / vol)乙醇诱导结肠炎。在第1天和第5天,溃疡面积,组织髓过氧化物酶(MPO)活性和管腔NE活性均增加,与急性炎症组织病理学变化相对应。这些急性炎症参数随后在第14天下降,并且慢性炎症组织病理学变化变得明显。直至第28天,均未观察到炎症复发。为评估我们的结肠炎模型,检查了泼尼松龙的作用。强的松龙在诱发结肠炎前一天口服一次,之后每天两次对动物进行治疗。尽管泼尼松龙对组织MPO活性影响很小,但泼尼松龙抑制溃疡面积和NE活性。此外,还检查了NE特异性抑制剂(ONO-6818)对我们TNBS诱导的结肠炎模型的影响。在皮下治疗研究中,在诱发结肠炎之前先给予ONO-6818。尽管ONO-6818对组织MPO活性影响很小,但在ONO-6818治疗组中溃疡面积和NE活性均降低。在诱发结肠炎后,用ONO-6818口服治疗后,证实了对溃疡区域和NE活性的抑制作用。我们得出的结论是,我们的结肠炎模型可用于研究结肠炎和NE之间的关系,并且抑制NE活动可以预防溃疡的发展。

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