DataSheet_1_A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis.pdf

BackgroundRadiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.
ObjectiveThe present study then aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis.
Material/MethodsC57BL/6 male mice were subjected to HDR (radiation source: iridium-192 [Ir-192]) through a cylindrical propylene tube inserted 2 cm far from the anal verge into the rectum. The animals received radiation doses once a day for three consecutive days (fractions of 9.5 Grays [Gy]), 3.0 mm far from the applicator surface. The sham group received only the applicator with no radiation source. The survival rate was recorded, and a colonoscopy was performed to confirm the tissue lesion development. Following euthanasia, samples of the rectum were collected for histopathology, cytokines dosage (IL-6 and KC), and immunohistochemical analysis (TNF-α and COX-2).
ResultsHDR significantly reduced animals’ survival ten days post first radiation exposure (14% survival vs. 100% in the non-irradiated group). Day seven was then used for further investigation. Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P < 0.05 vs. the control group). The tissue damage was accompanied by an inflammatory response, marked by increased KC and IL-6 tissue levels, and immunostaining for TNF-α and COX-2 (P < 0.05 vs. control group).
ConclusionsWe established a novel animal model of actinic proctitis induced by HDR brachytherapy, marked by inflammatory damage and low animal mortality.

背景：放射性直肠炎（radiation proctitis）在因盆腔恶性肿瘤（涵盖前列腺癌、妇科恶性肿瘤及直肠癌）接受放射治疗的癌症患者中，发病率为1%~20%。此类患者可表现为直肠不适、疼痛、分泌物增多及便血。值得关注的是，由于缺乏能够模拟该疾病的理想动物模型，预防性干预措施的疗效仍存在争议。
目的：本研究旨在构建一种高剂量率（high-dose-rate, HDR）近距离放射治疗诱导的放射性直肠炎小鼠模型。
材料与方法：选取C57BL/6雄性小鼠，通过距肛缘2 cm处插入直肠的圆柱形聚丙烯导管，给予高剂量率（HDR）放射照射，放射源为铱-192（iridium-192, Ir-192）。小鼠每日接受1次照射，连续3天，单次照射剂量为9.5戈瑞（Gray, Gy），照射距离距施源器表面3.0 mm。假手术组仅置入施源器，不放置放射源。记录小鼠生存率，并通过结肠镜检查确认组织损伤的形成。小鼠安乐处死后，采集直肠组织样本，用于组织病理学检测、细胞因子（白细胞介素-6 [IL-6]及KC）定量检测，以及免疫组化分析（肿瘤坏死因子-α [TNF-α]与环氧合酶-2 [COX-2]）。
结果：首次放射照射后10天，HDR组小鼠生存率显著下降（14% vs 未照射组的100%）。因此后续实验均选取照射后第7天进行分析。结肠镜检查与组织病理学结果证实，放射照射组小鼠出现直肠损伤（与对照组相比，P<0.05）。该组织损伤伴随炎症反应，表现为直肠组织中KC与IL-6水平升高，以及TNF-α、COX-2免疫染色阳性（与对照组相比，P<0.05）。
结论：本研究成功构建了一种新型的高剂量率近距离放射治疗诱导的放射性直肠炎动物模型，该模型以炎症性组织损伤为特征，且动物死亡率较低。