Department of Radiation Oncology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):242-50. doi: 10.1016/j.ijrobp.2009.07.1736.
To establish a novel mouse brachytherapy model with which to study the role of inflammation in the pathogenesis of radiation proctitis.
The distal rectums of BALB/c and C57BL/6 mice were irradiated with three to five fractions of 5.5 to 8 Gy. Tissues were harvested and evaluated for histopathology, using the radiation injury score (RIS). Cytokine mRNA expression was assessed using real-time PCR.
Fifty percent of the mice treated with 22 Gy delivered in four fractions of 5.5 Gy died as a result of anorectal stenosis and distal bowel obstruction prior to the time of scheduled sacrifice, with a latency period of 4 to 10 weeks for the BALB/c and 3 to 4 weeks for the C57BL/6 mice. The RISs were 7, 12, and 8 at 2, 6, and 11 weeks, respectively, in the BALB/c mice and was 8.7 in the C57BL/6 mice on week 6. A 100- to 300-fold increase in interleukin-1beta (IL-1beta) (p = 0.04) and IL-6 mRNA (p = 0.07) and a 5- to 6-fold increase in transforming growth factor (TGF) and tumor necrosis factor-alpha mRNA expression levels (p < 0.001 and p = 0.01) were observed at 2 to 6 weeks after radiation. Cytokine mRNA tissue expression correlated positively with radiation dose (p < 0.0001). The RIS correlated well with IL-1beta and IL-6 mRNA levels in the BALB/c mice and with IL-1beta, IL-6, and TGF mRNA levels in C57BL/6 mice. Analysis of receiver operating characteristic curve showed that IL-1beta and IL-6 have the largest area under the curve and therefore are good markers of radiation proctitis (p < 0.001).
Radiation-induced proctitis was associated with a dose-dependent, characteristic proinflammatory cytokine response pattern in a novel mouse model suitable for interventional studies.
建立一种新的小鼠近距离放射治疗模型，以研究炎症在放射性直肠炎发病机制中的作用。
BALB/c 和 C57BL/6 小鼠的直肠远端接受三到五次 5.5 至 8 Gy 的照射。使用放射损伤评分（RIS）评估组织的组织病理学变化。使用实时 PCR 评估细胞因子 mRNA 表达。
接受 22 Gy，4 次 5.5 Gy 照射的 50% BALB/c 小鼠和 3 至 4 次 5 Gy 照射的 C57BL/6 小鼠因肛门直肠狭窄和远端肠梗阻而在预定处死时间前死亡，潜伏期为 4 至 10 周。BALB/c 小鼠的 RIS 分别在 2、6 和 11 周时为 7、12 和 8，C57BL/6 小鼠在 6 周时为 8.7。在照射后 2 至 6 周，IL-1β（p = 0.04）和 IL-6 mRNA（p = 0.07）增加了 100 至 300 倍，TGF 和肿瘤坏死因子-α mRNA 表达水平增加了 5 至 6 倍（p < 0.001 和 p = 0.01）。细胞因子 mRNA 组织表达与辐射剂量呈正相关（p < 0.0001）。RIS 与 BALB/c 小鼠的 IL-1β 和 IL-6 mRNA 水平以及 C57BL/6 小鼠的 IL-1β、IL-6 和 TGF mRNA 水平密切相关。受试者工作特征曲线分析表明，IL-1β 和 IL-6 具有最大的曲线下面积，因此是放射性直肠炎的良好标志物（p < 0.001）。
在一种适合干预研究的新型小鼠模型中，放射性直肠炎与剂量依赖性、特征性促炎细胞因子反应模式相关。
