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17S‑环氧‑二十二碳五烯酸对葡聚糖硫酸钠诱导的 BALB/c 小鼠溃疡性结肠炎的保护作用。

Protective effect of 17S‑epoxy‑docosapentaenoic acid against dextran sulfate sodium induced ulcerative colitis in BALB/c mice.

机构信息

Korea Research Institute of Bioscience and Biotechnology, Microbial Biotechnology Research Center, Jeongeup, Jeollabuk‑do 56212, Republic of Korea.

College of Applied Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.

出版信息

Mol Med Rep. 2022 Sep;26(3). doi: 10.3892/mmr.2022.12794. Epub 2022 Jul 20.

Abstract

Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study demonstrated the protective effect of 7S,15R‑dihydroxy‑16S,17S‑epoxy‑docosapentaenoic acid (diHEP‑DPA), which had been previously synthesized, on a dextran sulfate sodium (DSS)‑induced BALB/c mouse model of UC. UC was induced with 4% DSS drinking water for 7 days. Initially, the anti‑inflammatory effect of diHEP‑DPA was confirmed by demonstrating that lipopolysaccharide‑stimulated THP1 cells treated with diHEP‑DPA decreased IL‑6, TNF‑α and nitrite levels by fluorescence‑activated cell sorting (FACS) and Griess reagent kit. The results indicated that the administration of diHEP‑DPA at 20 µg/kg significantly reduced the severity of colitis, as determined by hematoxylin and eosin staining. The levels of TNF‑α, IL‑6 and IL‑1β in the colon tissue and serum were significantly reduced in the diHEP‑DPA + DSS‑treated group compared with in the control group, as determined by FACS and ELISA kit. It was also observed that diHEP‑DPA decreased myeloperoxidase (MPO) and nitrite levels in the colon tissues of diHEP‑DPA + DSS‑treated mice, as indicated using commercial MPO and nitric oxide kits. The diHEP‑DPA+DSS‑treated mice also exhibited decreased expression levels of phosporylated (p)‑inhibitor κB protein, p‑p65 and inducible nitric oxide synthase in the colon tissue by inhibiting inflammation, which were measured by reverse transcription‑quantitative PCR and weatern blot analysis. Overall, the present study demonstrated the protective effect of diHEP‑DPA against a severe colitis condition .

摘要

溃疡性结肠炎(UC)难以根治,因为它会导致免疫系统功能障碍引起的消化道慢性炎症。本研究证明了先前合成的 7S,15R-二羟基-16S,17S-环氧二十二碳五烯酸(二HEP-DPA)对葡聚糖硫酸钠(DSS)诱导的 BALB/c 小鼠 UC 模型的保护作用。通过用 4% DSS 饮用水诱导 7 天来诱导 UC。最初,通过荧光激活细胞分选(FACS)和 Griese 试剂试剂盒证实,用二HEP-DPA 处理脂多糖刺激的 THP1 细胞可降低 IL-6、TNF-α 和亚硝酸盐水平,从而证实了二HEP-DPA 的抗炎作用。结果表明,用二HEP-DPA 以 20μg/kg 给药可显著减轻结肠炎的严重程度,通过苏木精和伊红染色来确定。通过 FACS 和 ELISA 试剂盒测定,与对照组相比,二HEP-DPA+DSS 处理组的结肠组织和血清中 TNF-α、IL-6 和 IL-1β 水平显著降低。还观察到二HEP-DPA 降低了二HEP-DPA+DSS 处理的小鼠结肠组织中的髓过氧化物酶(MPO)和亚硝酸盐水平,这是使用商业 MPO 和一氧化氮试剂盒测定的。二HEP-DPA+DSS 处理的小鼠还通过抑制炎症降低了结肠组织中磷酸化(p)-抑制因子 κB 蛋白、p-p65 和诱导型一氧化氮合酶的表达水平,这是通过逆转录-定量 PCR 和西方印迹分析测定的。总之,本研究证明了二HEP-DPA 对严重结肠炎的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/735c/9364144/cb7928961454/mmr-26-03-12794-g00.jpg

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