Cheng Jie, Li Fengsheng, Wang Guanjun, Guo Weiying, Huang Shan, Wang Brain, Li Cai, Jiang Qisheng, Cai Lu, Cui Jiuwei
Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pediatrics, Pediatric Research Institute, the University of Louisville, Louisville, KY, USA.
Dose Response. 2018 Sep 6;16(3):1559325818789843. doi: 10.1177/1559325818789843. eCollection 2018 Jul-Sep.
To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect the kidney from diabetes, type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age-matched normal mice received whole-body exposure to 12.5 or 25 mGy either every other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All these renal pathological and functional changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens. However, whole-body exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8 weeks provided a better prevention of diabetic nephropathy than other LDR regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no detectable effect on the kidney of normal mice, but whole-body exposure to normal mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and renal expression of collagen IV and fibronectin. These results suggest that whole-body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect the kidney from diabetes.
为探究全身低剂量辐射(LDR)预防糖尿病小鼠肾脏病变的最佳照射频率,通过多次注射低剂量链脲佐菌素诱导雄性C57BL/6J小鼠发生1型糖尿病。糖尿病小鼠或年龄匹配的正常小鼠每隔一天或每周接受12.5或25 mGy的全身照射,持续4或8周。糖尿病会降低尿肌酐水平,增加尿微量白蛋白、肾脏中3-硝基酪氨酸和4-羟基壬烯醛的蓄积,以及IV型胶原和纤连蛋白的肾脏表达。在所有照射方案下,糖尿病小鼠的所有这些肾脏病理和功能变化均因接受LDR照射而显著减轻。然而,糖尿病小鼠每周接受25 mGy全身照射以及每隔一天接受12.5 mGy全身照射持续8周,相较于其他LDR方案,能更好地预防糖尿病肾病。此外,正常小鼠每周接受25 mGy全身照射持续8周对肾脏无明显影响,但正常小鼠每隔一天接受12.5 mGy全身照射持续8周会增加尿微量白蛋白以及IV型胶原和纤连蛋白的肾脏表达。这些结果表明,每周25 mGy的全身LDR照射是预防糖尿病小鼠肾脏病变的最佳LDR条件。