Fractionated abdominal irradiation induces intestinal microvascular changes in an in vivo model of radiotherapy-induced gut toxicity
Fractionated abdominal irradiation induces intestinal microvascular changes in an in vivo model of radiotherapy-induced gut toxicity
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DOI：
10.1007/s00520-017-3601-3
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发表时间：
2017-06-01
影响因子：
3.1
通讯作者：
Gibson, Rachel J.
中科院分区：
文献类型：
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作者：
Stansborough, Romany L.;Bateman, Emma H.;Gibson, Rachel J.
放射治疗诱导的肠道毒性（RIGT）与腹泻、疼痛和直肠出血相关，可作为急性或慢性毒性发生。微血管系统已被证明是改变的RIGT的发展，但是，功能尚未确定。我们假设，微血管细胞的凋亡将发生在胃肠道分割照射后早期，随后是晚期微血管的变化，包括硬化和毛细血管扩张。雌性Dark Agglomerate大鼠进行了为期6周的分割放射治疗计划，每周3 x 2.5戈伊剂量定位于腹部。在第3、6和15周，检测肠组织的急性和慢性损伤标志物，包括形态学变化、胶原沉积、细胞凋亡和增殖，在第6和15周，空肠微血管细胞凋亡显著增加（分别为p = 0.0026和p = 0.0062）以及在6周和15周时在结肠中（分别为p < 0.0001和p = 0.0005）。从第3周开始，结肠微血管的组织学变化也出现了，包括固有层增厚和扩张，增厚，毛细血管扩张vessels.Findings的研究结果提供了证据，区域和时间特异性的变化，在肠道微血管的响应分次放疗，这可能在急性和慢性RIGT的发展中发挥作用。
Radiotherapy-induced gut toxicity (RIGT) is associated with diarrhoea, pain and rectal bleeding and can occur as an acute or chronic toxicity. The microvasculature has been shown to be altered in the development of RIGT; however, the features are not yet characterized. We hypothesized that apoptosis of microvascular cells would occur early in the gastrointestinal tract following fractionated irradiation, followed by late microvascular changes, including sclerosis and telangiectasis.Female Dark Agouti rats were treated with a 6-week fractionated radiation schedule of 3 x 2.5 Gy doses per week localized to the abdomen. At 3, 6 and 15 weeks, the intestines were assessed for markers of acute and chronic injury including morphological changes, collagen deposition, apoptosis and proliferation.Apoptosis of microvascular cells significantly increased at 6 and 15 weeks in the jejunum (p = 0.0026 and p = 0.0062, respectively) and at 6 and 15 weeks in the colon (p < 0.0001 and p = 0.0005, respectively) in rats receiving fractionated radiation to the abdomen. Histopathological changes of the colon microvasculature were also seen from week 3, including thickening of the lamina propria and dilated, thickened, telangiectatic vessels.Findings of this study provide evidence of regional and timing-specific changes in the intestinal microvasculature in response to fractionated radiotherapy which may play a role in development of both acute and chronic RIGT.