Institute of Anatomy, University of Fribourg, Fribourg, Switzerland.
Int J Radiat Oncol Biol Phys. 2011 Aug 1;80(5):1522-32. doi: 10.1016/j.ijrobp.2011.03.018.
To explore the effects of microbeam radiation (MR) on vascular biology, we used the chick chorioallantoic membrane (CAM) model of an almost pure vascular system with immature vessels (lacking periendothelial coverage) at Day 8 and mature vessels (with coverage) at Day 12 of development.
CAMs were irradiated with microplanar beams (width, ∼25 μm; interbeam spacing, ∼200 μm) at entrance doses of 200 or 300 Gy and, for comparison, with a broad beam (seamless radiation [SLR]), with entrance doses of 5 to 40 Gy.
In vivo monitoring of Day-8 CAM vasculature 6 h after 200 Gy MR revealed a near total destruction of the immature capillary plexus. Conversely, 200 Gy MR barely affected Day-12 CAM mature microvasculature. Morphological evaluation of Day-12 CAMs after the dose was increased to 300 Gy revealed opened interendothelial junctions, which could explain the transient mesenchymal edema immediately after irradiation. Electron micrographs revealed cytoplasmic vacuolization of endothelial cells in the beam path, with disrupted luminal surfaces; often the lumen was engorged with erythrocytes and leukocytes. After 30 min, the capillary plexus adopted a striated metronomic pattern, with alternating destroyed and intact zones, corresponding to the beam and the interbeam paths within the array. SLR at a dose of 10 Gy caused growth retardation, resulting in a remarkable reduction in the vascular endpoint density 24 h postirradiation. A dose of 40 Gy damaged the entire CAM vasculature.
The effects of MR are mediated by capillary damage, with tissue injury caused by insufficient blood supply. Vascular toxicity and physiological effects of MR depend on the stage of capillary maturation and appear in the first 15 to 60 min after irradiation. Conversely, the effects of SLR, due to the arrest of cell proliferation, persist for a longer time.
为了探究微束辐射(MR)对血管生物学的影响,我们使用鸡胚绒毛尿囊膜(CAM)模型,该模型具有几乎完全由不成熟血管(缺乏血管内皮细胞覆盖)构成的血管系统,在发育的第 8 天,这些不成熟血管会逐渐发育为成熟血管(具有覆盖物)。
将 CAM 用微束(宽度约 25μm,束间距约 200μm)进行照射,束入口剂量为 200 或 300Gy,并与宽束(无缝辐射[SLR])进行比较,入口剂量为 5 至 40Gy。
在 200GyMR 照射后 6 小时对第 8 天的 CAM 血管进行体内监测,发现不成熟的毛细血管丛几乎完全被破坏。相反,200GyMR 对第 12 天的 CAM 成熟微血管几乎没有影响。当剂量增加到 300Gy 时,对第 12 天的 CAM 进行形态学评估,发现内皮细胞的细胞间连接开放,这可以解释照射后立即出现的短暂间充质水肿。电子显微镜显示,在束路径中内皮细胞的细胞质有空泡化,管腔表面破裂;管腔经常充满红细胞和白细胞。30 分钟后,毛细血管丛呈现出条纹状的节拍模式,束和束之间的交替破坏和完整区域,与束和束之间的阵列相对应。10Gy 的 SLR 会导致生长迟缓,导致照射后 24 小时血管终点密度显著降低。40Gy 的剂量会破坏整个 CAM 血管系统。
MR 的影响是通过毛细血管损伤介导的,组织损伤是由于血液供应不足引起的。MR 的血管毒性和生理效应取决于毛细血管成熟的阶段,并在照射后 15 至 60 分钟内出现。相反,由于细胞增殖停滞,SLR 的影响会持续更长时间。