Egger B, Bajaj-Elliott M, MacDonald T T, Inglin R, Eysselein V E, Büchler M W
Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.
Digestion. 2000;62(4):240-8. doi: 10.1159/000007822.
BACKGROUND/AIMS: In our experience with the acute murine dextran sodium sulphate (DSS) model of experimental colitis, we noted both interstrain and interanimal variations in daily water consumption. One might critically question whether observed differences in injuries are just a dose dependency phenomenon reflecting variations in DSS intake. To clarify this important topic, we performed a dose and concentration dependency study of DSS in Balb/c mice. We also determined Th1 and Th2 cytokine levels to compare the cytokine profile to that from inflammatory bowel disease (IBD).
In four groups (14 animals each group) different concentrations of DSS (0, 2.5, 5 and 7.5%) were given for 7 days ad libitum. Mucosal injury of the entire colon was histologically assessed and graded. Cytokine levels were determined by competitive quantitative RT-PCR.
A linear increase in the crypt damage score was noted with increasing concentrations (0, 4.9 +/- 0.7, 11.9 +/- 0.5 and 18.9 +/- 1.3, respectively), but the total dose of DSS intake did not correlate with mucosal damage. Progressive upregulation in the transcripts for Th1 cytokines (IL-12, IFN-gamma, IL-1, TNF-alpha) was observed with increasing dosage of DSS. Interestingly, an increase in IL-10, but not IL-4 mRNA transcripts was also noted.
Acute DSS-induced mucosal injury is dependent on the administered DSS water concentration but not on the consumed DSS dose. The cytokine profile is a classic Th1 response and is similar to that of various inflammatory conditions in the colon.
Minor variations in fluid consumption do not affect the severity of DSS-induced injury in mice. The acute murine DSS colitis model is useful for studying the pathophysiological aspects of colonic inflammatory diseases as IBD and for evaluating new potential therapeutic agents
背景/目的：根据我们在急性小鼠葡聚糖硫酸钠（DSS）实验性结肠炎模型中的经验，我们注意到每日饮水量存在品系间和动物间的差异。有人可能会严重质疑观察到的损伤差异是否仅仅是反映DSS摄入量变化的剂量依赖性现象。为了阐明这个重要问题，我们在Balb/c小鼠中进行了DSS的剂量和浓度依赖性研究。我们还测定了Th1和Th2细胞因子水平，以将细胞因子谱与炎症性肠病（IBD）的细胞因子谱进行比较。
将四组（每组14只动物）给予不同浓度的DSS（0、2.5、5和7.5%），自由饮用7天。对整个结肠的黏膜损伤进行组织学评估并分级。通过竞争性定量RT-PCR测定细胞因子水平。
随着浓度增加（分别为0、4.9±0.7、11.9±0.5和18.9±1.3），隐窝损伤评分呈线性增加，但DSS摄入的总剂量与黏膜损伤无关。随着DSS剂量增加，观察到Th1细胞因子（IL-12、IFN-γ、IL-1、TNF-α）转录本的逐步上调。有趣的是，还注意到IL-10 mRNA转录本增加，但IL-4 mRNA转录本未增加。
急性DSS诱导的黏膜损伤取决于给予的DSS水浓度，而不取决于消耗的DSS剂量。细胞因子谱是典型的Th1反应，与结肠中的各种炎症情况相似。
液体摄入量的微小变化不会影响小鼠中DSS诱导损伤的严重程度。急性小鼠DSS结肠炎模型可用于研究IBD等结肠炎症性疾病的病理生理学方面，并用于评估新的潜在治疗药物。
