Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Inflamm Bowel Dis. 2011 Mar;17(3):742-6. doi: 10.1002/ibd.21423. Epub 2010 Sep 27.
Hypoxia has been reported to be associated with the colonic inflammation observed in a chemically induced mouse model of self-limiting colitis, suggesting that low tissue oxygen tension may play a role in the pathophysiology of inflammatory tissue injury. However, no studies have been reported evaluating whether tissue hypoxia is associated with chronic gut inflammation. Therefore, the objective of the present study was to determine whether hypoxia is produced within the colon during the development of chronic gut inflammation.
Adoptive transfer of CD4(+) T cells obtained from interleukin-10-deficient (IL-10(-/-)) mice into lymphopenic recombinase-activating gene-1-deficient (RAG(-/-)) mice induces chronic colonic inflammation, with the inflammation ranging from mild to severe as determined by blinded histological analyses. Colonic blood flow, hematocrit, and vascular density were determined using standard protocols, whereas tissue hypoxia was determined using the oxygen-dependent probe pimonidazole.
Adoptive transfer of IL-10(-/-) CD4(+) T cells into RAG(-/-) recipients induced chronic colonic inflammation that ranged from mild to severe at 8 weeks following T-cell transfer. The colitis was characterized by bowel wall thickening, goblet cell dropout, and inflammatory infiltrate. Surprisingly, we found that animals exhibiting mild colonic inflammation had increased hypoxia and decreased systemic hematocrit, whereas mice with severe colitis exhibited levels of hypoxia and hematocrit similar to healthy controls. In addition, we observed that the extent of hypoxia correlated inversely with hematocrit and vascular density.
Changes in hematocrit, vascular density, and inflammatory state appear to influence the extent of tissue oxygenation in the T-cell-mediated model of chronic gut inflammation.
据报道，缺氧与化学诱导的自限性结肠炎小鼠模型中观察到的结肠炎症有关，这表明低组织氧张力可能在炎症组织损伤的病理生理学中发挥作用。然而，目前尚未有研究评估组织缺氧是否与慢性肠道炎症有关。因此，本研究的目的是确定在慢性肠道炎症发展过程中，结肠内是否会产生缺氧。
将白细胞介素-10 缺陷（IL-10(-/-)）小鼠来源的 CD4(+)T 细胞过继转移到重组激活基因-1 缺陷（RAG(-/-)）小鼠中，会诱导慢性结肠炎症，通过盲法组织学分析确定炎症从轻度到重度不等。使用标准方案测定结肠血流、红细胞压积和血管密度，而使用氧依赖性探针 pimonidazole 测定组织缺氧。
将 IL-10(-/-) CD4(+)T 细胞过继转移到 RAG(-/-)受者中，会在 T 细胞转移后 8 周诱导慢性结肠炎症，从轻度到重度不等。结肠炎的特征是肠壁增厚、杯状细胞丢失和炎症浸润。令人惊讶的是，我们发现轻度结肠炎的动物有增加的缺氧和降低的系统红细胞压积，而严重结肠炎的小鼠的缺氧和红细胞压积水平与健康对照相似。此外，我们观察到缺氧程度与红细胞压积和血管密度呈负相关。
红细胞压积、血管密度和炎症状态的变化似乎会影响 T 细胞介导的慢性肠道炎症模型中组织氧合的程度。
