基于小动物照射研究平台建造C57BL6/J小鼠急性放射性肠炎精准模型研究

目的基于小动物照射研究平台建造C57BL6/J小鼠放射性肠炎精准模型。方法将48只雌性小鼠随机均分为空白对照组、6 Gy照射组、9 Gy照射组及12 Gy照射组4组。基于SARRP,照射组小鼠接受全腹单次照射,剂量率为4 Gy/min。观察小鼠一般情况、体重、小肠病理改变。结果CT扫描后,勾画靶区及正常组织,根据4个预计划靶区剂量分布及脊髓保护,采用等中心水平对穿照射方案。6、9、12 Gy组平均照射时间分别为163、252、328 s。照射后15天6、9、12 Gy组小鼠的生存率分别为100%、100%、50%;照射后第5天6、9、12 Gy组小鼠体重较空白对照组明显下降(P=0.035、P=0.002、P<0.001),10天后逐渐上升。随着照射剂量增加,肠黏膜绒毛和腺体损伤逐渐加重。与较空白对照组相比,9、12 Gy组绒毛长度明显缩短(P<0.001);照射组肠壁厚度明显变薄(P<0.001)。结论SARRP在小鼠放射性肠炎模型建造中能够提供精准的靶区定位、计划的筛选和精确的剂量交付。6~9 Gy的单次全腹水平对穿照射能够成功地建造C57BL6/J雌性小鼠的急性放射性肠炎模型。

Establishment of an accurate C57BL6/J mouse model of acute radiation-induced enteritis based on small animal radiation research platform

Objective To establish an accurate C57BL6/J mouse model of acute radiation-induced enteritis based on small animal radiation research platform (SARRP). Methods Forty-eight female mice were randomly divided into the following four groups:blank control group, 6Gy irradiation group, 9Gy irradiation group and 12Gy irradiation group. Based on the SARRP, the mice in the irradiation groups were exposed to a single fraction dose of 6Gy, 9Gy and 12Gy at a dose rate of 4Gy/min, respectively. The general condition, body weight andpathological changes of the small intestine of mice were observed. ResultsAfter CT scanning, the target area and normal tissues were delineated. According to the dose distribution of the target area and the protection of spinal cord, the AP-PA field irradiation scheme at the isocentric level was adopted. The average irradiation time in the 6, 9 and 12Gy groups was 163, 252 and 328 seconds, respectively.The survival rates of mice in the 6, 9 and 12 Gy groups were 100%, 100% and 50% 15 days after irradiation.The body weight of mice in the 6Gy (P=0.035), 9Gy (P=0.002) and 12Gy groups (P<0.001) was decreased significantly on the 5^th day after irradiation, and gradually increased on the 10^th day. With the increase of irradiation dose, the villus and gland injury was aggravated. Compared with the blank control group, the villus length in the 9 and 12Gy groups was significantly shorter (both P<0.001), and theintestinal wall thickness in the irradiation groups was significantly thinner (all P<0.001). Conclusions ARRP can provide accurate target location, planned screening and accurate dose delivery in the establishment of C57BL6/J mouse model of acute radiation-induced enteritis. The C57BL6/J mouse model of acute radiation-induced enteritis can be successfully established by a single fraction total-abdominal irradiation of 6-9Gy.