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通过灌胃给予葡聚糖硫酸钠诱导的实验性溃疡性结肠炎小鼠模型的建立与评价

Establishment and Evaluation of a Mouse Model of Experimental Ulcerative Colitis Induced by the Gavage Administration of Dextran Sulfate Sodium.

作者信息

Wang Dan, Chen Wei, Cao Jie, Si Luqin, Chen Zehong

机构信息

Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Pharmaceutics, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.

出版信息

Biomedicines. 2024 Aug 5;12(8):1764. doi: 10.3390/biomedicines12081764.

Abstract

Given the critical role of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse models in the appraisal of associated therapeutic drugs, the optimization of the administration method and dosages is of paramount importance. Therefore, UC was induced in mice through the gavage administration of a DSS solution instead of free drinking water. The effects of varying daily dosages (2, 4, 6, and 8 g/kg) and frequencies (once or twice) of administration on the body weight and survival rate of the model mice were evaluated. Concurrently, the inflammatory indicators and tissue sections of the model mice were thoroughly evaluated. The results revealed that when the daily dosage reached 8 g/kg, the dosage exhibited a high level of toxicity, resulting in a high mortality rate among the mice. The DSS administration of 6 g/kg*2 not only elicited conspicuous symptoms, significant weight loss, substantial shortening of the colon, and significant changes in various inflammatory indicators, such as myeloperoxidase (MPO), nitric oxide (NO), reactive oxygen species (ROS), and glutathione (GSH), but it also maintained a high survival rate in the UC mice. The findings from this experiment lay a solid experimental foundation for future research on drugs intended for the treatment of UC.

摘要

鉴于葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)小鼠模型在相关治疗药物评估中的关键作用,优化给药方法和剂量至关重要。因此,通过给小鼠灌胃DSS溶液而非自由饮用含DSS的水来诱导UC。评估了不同每日剂量(2、4、6和8 g/kg)和给药频率(一次或两次)对模型小鼠体重和存活率的影响。同时,对模型小鼠的炎症指标和组织切片进行了全面评估。结果显示,当日剂量达到8 g/kg时,该剂量表现出高毒性,导致小鼠死亡率很高。6 g/kg×2的DSS给药不仅引发明显症状、显著体重减轻、结肠显著缩短以及多种炎症指标(如髓过氧化物酶(MPO)、一氧化氮(NO)、活性氧(ROS)和谷胱甘肽(GSH))的显著变化,而且在UC小鼠中保持了较高的存活率。本实验结果为未来治疗UC药物的研究奠定了坚实的实验基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f638/11352140/6d677b174d35/biomedicines-12-01764-g001.jpg

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