Followill D S, Kester D, Travis E L
Department of Physics, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Radiat Res. 1993 Nov;136(2):280-8.
These studies were undertaken to determine the relationship between acute mucosal damage and late obstructions in the colorectal region in the mouse after exposure to radiation. Radiation doses that either permanently depleted the mucosal epithelial cells or spared the mucosal lining by allowing epithelial regeneration were used. The distal 2.5 cm of colon and rectum of male C3Hf/Kam mice was irradiated with either a range of single doses (15-35 Gy) or two equal doses ranging from 9.75 to 14.75 Gy separated by 10 days. The time of onset and the incidence of obstructions and strictures in the bowel were recorded as a function of dose and time after irradiation. Acute damage in the mucosa and subsequent histological changes in the bowel were documented by sequential histological studies. Doses greater than 20 Gy caused acute crypt depletion followed by nonproductive attempts at regeneration and repopulation that culminated in persistent epithelial denudation. In these mice, obstructions appeared as early as 4 weeks and were characterized histologically by a mucosal ulceration extending deep into the muscularis. Single doses of less than 20 Gy and the split doses produced acute crypt cell depletion followed by successful regeneration, repopulation, and restoration of the colonic mucosa. In these mice, obstructions did not appear until at least 40 weeks after irradiation and were characterized by an intact mucosa with a thickened and fibrotic submucosa. Animals given a single dose of 20 Gy developed obstructions throughout the duration of the experiment. Those obstructions that occurred before 6 months were characterized by ulcerations, whereas those that appeared after this time exhibited only fibrosis in the submucosa with no mucosal ulceration. Based on these data, we suggest that two types of late obstructions occur in the bowel, one that depends on persistent epithelial denudation, i.e., a "consequential" response, and the other in the absence of epithelial denudation, i.e., a true late effect.
开展这些研究是为了确定小鼠结肠直肠区域在受到辐射后急性黏膜损伤与晚期梗阻之间的关系。使用了能使黏膜上皮细胞永久耗竭的辐射剂量，以及通过允许上皮再生而使黏膜层得以保留的辐射剂量。对雄性C3Hf/Kam小鼠的结肠和直肠远端2.5厘米进行一系列单剂量（15 - 35 Gy）照射，或分两次给予剂量范围为9.75至14.75 Gy且间隔10天的同等剂量照射。记录肠道梗阻和狭窄的发病时间及发生率，作为照射后剂量和时间的函数。通过连续的组织学研究记录黏膜的急性损伤以及随后肠道的组织学变化。大于20 Gy的剂量导致急性隐窝耗竭，随后是再生和再增殖的无效尝试，最终导致持续性上皮剥脱。在这些小鼠中，梗阻最早在4周时出现，组织学特征为黏膜溃疡深入肌层。小于20 Gy的单剂量和分次剂量导致急性隐窝细胞耗竭，随后是结肠黏膜的成功再生、再增殖和恢复。在这些小鼠中，梗阻直到照射后至少40周才出现，组织学特征为黏膜完整，黏膜下层增厚且纤维化。给予单剂量20 Gy的动物在整个实验过程中都出现了梗阻。6个月前出现的梗阻以溃疡为特征，而在此之后出现的梗阻仅表现为黏膜下层纤维化，无黏膜溃疡。基于这些数据，我们认为肠道会出现两种类型的晚期梗阻，一种取决于持续性上皮剥脱，即“继发性”反应，另一种则在上皮未剥脱的情况下出现，即真正的晚期效应。
