In vivo detection of morphological and microvascular changes of the colon in association with colitis using fiberoptic confocal Imaging (FOCI)
In vivo detection of morphological and microvascular changes of the colon in association with colitis using fiberoptic confocal Imaging (FOCI)
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DOI：
10.1023/a:1020631220599
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发表时间：
2002-11-01
影响因子：
3.1
通讯作者：
King, RG
中科院分区：
文献类型：
--
作者：
McLaren, WJ;Anikijenko, P;King, RG
本研究采用一种成熟的炎症性肠病（IBD）啮齿动物模型，研究了溃疡性结肠炎（UC）相关的结肠粘膜微血管的变化。将结果与组织形态学的微观变化进行比较，以建立微循环功能障碍与IBD病理学之间的时间关系。通过口服含5%葡聚糖硫酸钠（DSS）的饮用水诱导大鼠轻度结肠炎。对照动物可自由饮水。在口服摄入DSS 3、5和7天后，将麻醉的大鼠剖腹。然后使用光纤共聚焦成像（FOCI;激发488 nm氩离子激光，检测高于515 nm）检查远端结肠的粘膜表面。局部应用荧光染料盐酸四环素后，检查粘膜结构的变化。四环素盐酸盐是一种广泛应用于临床的抗生素，可使粘膜表面的隐窝成像。在微血管结构的空间变化进行了评估后，静脉注射异硫氰酸荧光素葡聚糖（FITC-葡聚糖）。共聚焦图像与临床参数相关，包括体重减轻、潜血和大便粘稠度。在第3天结肠炎时检测到结肠上皮的衰减。结肠炎第5天和第7天检测到包括隐窝丢失、隐窝变形和炎性细胞浸润的形态学变化。双通道成像显示粘膜毛细血管网络勾勒出对照组织中粘液分泌腺的基质范围。实验性结肠炎导致弥漫性血管过多和毛细血管迂曲。在结肠炎第5天首次检测到血管渗漏增加的证据（FITC-葡聚糖从管腔渗漏）。DSS摄入7天后，血管的正常蜂窝状图案和毛细血管扩张明显完全破坏。这些研究结果表明，溃疡性结肠炎的发病机制与血管结构的变化，在体内使用共聚焦显微镜证明。
Using a well-established rodent model of inflammatory bowel disease (IBD), the present study examined changes in the microvasculature of the colonic mucosa in association with ulcerative colitis (UC). The results were compared to microscopic alterations in tissue morphology to establish a temporal relationship between microcirculatory dysfunction and IBD pathology. Mild colitis was induced in rats by the oral consumption of 5% dextran sulfate sodium (DSS) in drinking water. Control animals were provided with water ad libitum. After 3, 5, and 7 days of oral ingestion of DSS, anesthetized rats were laparotomized. The mucosal surface of the distal colon was then examined using fiber optic confocal imaging (FOCI; excitation 488 nm argon ion laser, detection above 515 nm). Changes in the mucosal architecture were examined following the topical application of the fluorescent dye, tetracycline hydrochloride. Tetracycline hydrochloride, an antibiotic used widely in clinical medicine, enabled imaging of the crypts at the surface of the mucosa. Spatial changes in the microvascular structure were assessed following the intravenous administration of fluorescein isothiocyanate dextran (FITC-dextran). Confocal images were correlated with clinical parameters, including weight loss, occult blood, and stool consistency. Attenuation of the colonic epithelium was detected on day 3 colitis. Morphological changes including crypt loss, crypt distortion, and inflammatory cell infiltrate were detected on day 5 and day 7 colitis. Dual channel imaging showed the mucosal capillary network outlining the stromal confines of the mucus-secreting glands in control tissue. Experimental colitis resulted in diffuse hypervascularity and tortuosity of the capillary vessels. Evidence of increased vessel leakiness (leakage of FITC-dextran from the lumen) was first detected on day 5 colitis. Complete disruption of the normal honeycomb pattern of the vessels and capillary dilation was evident after 7 days of DSS ingestion. These findings suggest that the pathogenesis of ulcerative colitis is associated with changes in the vascular architecture as demonstrated in vivo using confocal microscopy.