Tsogbadrakh Bodokhsuren, Lee Minyoung, Jung Joo-Ae, Choi Yang-Kyu, Lee Yong Jin, Seo Jin-Hee
Institute of Breast Cancer Precision Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Laboratory Animal Team, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
Biochem Biophys Res Commun. 2025 Jan;745:151264. doi: 10.1016/j.bbrc.2024.151264. Epub 2024 Dec 28.
Radiation therapy is crucial for cancer treatment, but it often causes tissue damage. The kidney, which is sensitive to radiation, is under-researched in this context. This study aimed to develop a mouse model for radiation-induced acute kidney injury (AKI) using a small animal radiation research platform (SARRP) to mimic clinical radiation conditions. To establish the optimal AKI model, six-week-old male BALB/c mice were irradiated at doses of 5, 10, 20, and 30 Gy. Based on serum creatinine and blood urea nitrogen (BUN) levels, as well as immunohistochemical staining for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), a 30 Gy dose was selected. This dose was applied in three ways: (1) single arc after a CT scan (K1, one kidney), (2) two arcs and two static beams after a CT scan (K2, both kidneys), and (3) abdominal irradiation after a single X-ray image (AI, including the kidneys). AKI was assessed 5 days post-irradiation. All irradiated groups exhibited more weight loss compared to the sham group, with the K2 group showing the most significant loss (p < 0.001 vs. K1, p < 0.05 vs. AI). The K2 group also demonstrated a significant reduction in kidney weight (p < 0.05 vs. K1) and higher serum BUN levels (p < 0.05 vs. sham, p < 0.01 vs. K1). Histopathological analysis revealed severe damage in the K2 group, including granular casts and tubular necrosis. The K2 group had elevated NGAL, KIM-1, γ-H2AX, malondialdehyde, and caspase-3 levels, indicating increased AKI severity and DNA damage. The SARRP-created AKI model effectively targeted renal tissue while sparing extrarenal tissues, offering a more clinically relevant model compared to traditional methods. This model bridges the gap between clinical and preclinical studies, enhancing the accuracy and relevance of research on radiation-induced kidney injury.
放射治疗对癌症治疗至关重要，但它常常会导致组织损伤。肾脏对辐射敏感，在这方面的研究较少。本研究旨在利用小动物辐射研究平台（SARRP）开发一种辐射诱导急性肾损伤（AKI）的小鼠模型，以模拟临床辐射情况。为建立最佳的AKI模型，对六周龄雄性BALB/c小鼠分别给予5、10、20和30 Gy的辐射剂量。根据血清肌酐和血尿素氮（BUN）水平，以及中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和肾损伤分子-1（KIM-1）的免疫组化染色结果，选择了30 Gy的剂量。该剂量通过三种方式给予：（1）CT扫描后单弧照射（K1，一侧肾脏），（2）CT扫描后双弧和两束静态光束照射（K2，双侧肾脏），（3）单次X射线图像后腹部照射（AI，包括双侧肾脏）。在照射后5天评估AKI情况。与假照射组相比，所有照射组体重减轻更明显，其中K2组体重减轻最为显著（与K1组相比，p < 0.001；与AI组相比，p < 0.05）。K2组肾脏重量也显著降低（与K1组相比，p < 0.05），血清BUN水平更高（与假照射组相比，p < 0.05；与K1组相比，p < 0.01）。组织病理学分析显示K2组损伤严重，包括颗粒管型和肾小管坏死。K2组NGAL、KIM-1、γ-H2AX、丙二醛和半胱天冬酶-3水平升高，表明AKI严重程度增加和DNA损伤。利用SARRP创建的AKI模型有效靶向肾组织，同时保护肾外组织，与传统方法相比，提供了一个更具临床相关性的模型。该模型弥合了临床研究和临床前研究之间的差距，提高了辐射诱导肾损伤研究的准确性和相关性。
