通过口服 5,6-二羟基-8Z,11Z,14Z,17Z-二十碳四烯酸在小鼠中有效减轻葡聚糖硫酸钠诱导的结肠炎,International Journal of Molecular Sciences

当前位置： X-MOL 学术 › Int. J. Mol. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

通过口服 5,6-二羟基-8Z,11Z,14Z,17Z-二十碳四烯酸在小鼠中有效减轻葡聚糖硫酸钠诱导的结肠炎
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2021-08-27 , DOI: 10.3390/ijms22179295
Shinya Takenouchi ₁ , Daiki Imai ₁ , Tatsuro Nakamura ₁ , Takahisa Murata ₁

Affiliation

5,6-二羟基-8Z,11Z,14Z,17Z-二十碳四烯酸 (5,6-DiHETE) 是一种源自二十碳五烯酸的新发现的生物活性抗炎脂质介质，具有多种功能。在这里，我们评估了口服 5,6-DiHETE 在促进葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎愈合方面的潜力。我们在小鼠口服给药前和给药后 0.5、1、3 和 6 小时（150 或 600 μg/kg）测量了 5,6-DiHETE 的血浆浓度。小鼠通过 DSS（2% 在饮用水中 4 天）发展为结肠炎，并从第 9 天到第 14 天口服 5,6-DiHETE（150 或 600 μg/kg/天）。接下来，评估粪便硬度和出血，以及在第 14 天通过 H&E 染色解剖的结肠。5,6-DiHETE 的血浆浓度达到 25.05 或 44.79 ng/mL 0。给药后5 h分别为150或600 μg/kg，随后逐渐减量。5,6-DiHETE 的半衰期估计为 1.25-1.63 小时。腹泻在第 3 天后恶化，并在第 5 天达到高峰，然后逐渐恢复。第 14 天的组织学评估显示小鼠出现 DSS 介导的粒细胞浸润、粘膜糜烂、粘膜下水肿和隐窝脓肿。口服 150 或 600 μg/kg/天的 5,6-DiHETE 加速了 DSS 诱导的腹泻的恢复并显着改善了结肠炎症。600 μg/kg/天 5,6-DiHETE 的治疗效果略强于 150 μg/kg/天。我们的研究揭示了通过口服 5,6-DiHETE 剂量依赖性地减轻小鼠 DSS 诱导的结肠炎，从而表明治疗潜力为 5，

"点击查看英文标题和摘要"

Efficient Attenuation of Dextran Sulfate Sodium-Induced Colitis by Oral Administration of 5,6-Dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic Acid in Mice

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived newly discovered bioactive anti-inflammatory lipid mediator having diverse functions. Here, we assessed the potential of orally administered 5,6-DiHETE in promoting healing of dextran sulfate sodium (DSS)-induced colitis in mice. We measured the plasma concentrations of 5,6-DiHETE in untreated mice before and 0.5, 1, 3, and 6 h after its oral administration (150 or 600 μg/kg) in mice. Mice developed colitis by DSS (2% in drinking water for 4 days), and 5,6-DiHETE (150 or 600 μg/kg/day) was orally administered from day 9 to 14. Next, the faecal hardness and bleeding were assessed, and the dissected colons on day 14 via H&E staining. The plasma concentration of 5,6-DiHETE reached 25.05 or 44.79 ng/mL 0.5 h after the administration of 150 or 600 μg/kg, respectively, followed by a gradual decrease. The half-life of 5,6-DiHETE was estimated to be 1.25–1.63 h. Diarrhoea deteriorated after day 3 and peaked on day 5, followed by a gradual recovery. Histological assessment on day 14 showed DSS-mediated granulocyte infiltration, mucosal erosion, submucosal edema, and cryptal abscesses in mice. Oral administration of 150 or 600 μg/kg/day of 5,6-DiHETE accelerated the recovery from the DSS-induced diarrhoea and significantly ameliorated colon inflammation. The therapeutic effect of 600 μg/kg/day 5,6-DiHETE was slightly stronger than that by 150 μg/kg/day. Our study reveals attenuation of DSS-induced colitis in mice by the oral administration of 5,6-DiHETE dose-dependently, thereby suggesting a therapeutic potential of 5,6-DiHETE for inflammatory bowel disease.

更新日期：2021-08-27

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文