C57BL/6小鼠右旋糖酐硫酸钠诱导的亚急性结肠炎模型中适应性免疫反应的参与。

IF 1.9 Q3 PHARMACOLOGY & PHARMACY Drug Discoveries and Therapeutics Pub Date : 2023-09-15 Epub Date: 2023-07-12 DOI:10.5582/ddt.2023.01015
Jing Li, Fangzhou Dou, Shasha Hu, Jianjun Gao
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引用次数: 0

摘要

炎症性肠病(IBD)是一种非特异性的慢性肠道炎症性疾病。药物治疗是IBD的主要治疗策略;然而,目前的药物有一定的局限性,如无效和诱导耐受的倾向,因此需要开发创新药物来满足治疗要求。用约3%右旋糖酐硫酸钠(DSS)溶液诱导的急性结肠炎模型已广泛用于临床前药物开发。尽管如此,该模型仍有一些缺点,包括疾病进展迅速导致一些小鼠死亡,以及小鼠的炎症特征与人类IBD的病理特征之间的差异。目前的研究发现,自由摄入较低浓度DSS溶液(1-1.5%)10-15天的小鼠表现出较轻的结肠炎症状。持续服用DSS溶液15-20天导致结肠组织慢性炎症,同时Th1细胞比例显著增加,表明参与了适应性免疫反应。随后,用美沙拉秦或Centella三萜类药物治疗小鼠,同时服用DSS溶液10天。与对照组相比,接受治疗的小鼠在体重和结肠长度方面有显著改善。这种亚急性模型的优点包括实验小鼠的死亡率最低,并且小鼠的肠粘膜炎症与人类IBD的病理特征相似,从而能够评估针对IBD的药物疗效。
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Involvement of adaptive immune responses in a model of subacute colitis induced with dextran sulfate sodium in C57BL/6 mice.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disorder. Pharmacotherapy serves as the main treatment strategy for IBD; however, the current medications have certain limitations, such as inefficacy and a tendency to induce tolerance, thereby requiring the development of innovative drugs to fulfill therapeutic requirements. A model of acute colitis induced with a solution of approx. 3% dextran sulfate sodium (DSS) has been widely used in preclinical drug development. Nevertheless, this model has some drawbacks, including rapid disease progression leading to mortality in some mice and disparities between the inflammatory characteristics of mice and the pathological features of human IBD. The current study found that mice freely consuming a lower concentration of a DSS solution (1-1.5%) for 10-15 days exhibited milder colitis symptoms. Continued consumption of the DSS solution for 15-20 days resulted in chronic inflammation in colon tissue, accompanied by a significant increase in the proportion of Th1 cells, indicating the involvement of adaptive immune responses. Subsequently, mice were treated with mesalazine or Centella triterpenes while concurrently consuming the DSS solution for 10 days. The treated mice had significant improvements in body weight and colon length compared to the control group. The advantages of this subacute model include minimal mortality among experimental mice and the fact that intestinal mucosal inflammation in mice resembles the pathological features of human IBD, enabling the assessment of drug efficacy against IBD.

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来源期刊
Drug Discoveries and Therapeutics
Drug Discoveries and Therapeutics PHARMACOLOGY & PHARMACY-
CiteScore
3.20
自引率
3.20%
发文量
51
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