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连续低剂量率γ射线照射对 2 型糖尿病模型小鼠糖尿病肾病的抑制作用。

Suppressive effects of continuous low-dose-rate γ irradiation on diabetic nephropathy in type II diabetes mellitus model mice.

机构信息

Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado Kita, Komae, Tokyo 201-8511, Japan.

出版信息

Radiat Res. 2011 Sep;176(3):356-65. doi: 10.1667/rr2559.1. Epub 2011 Jun 30.

Abstract

It has been proposed that the development of diabetic nephropathy is caused in large part by oxidative stress. We previously showed that continuous exposure of mice to low-dose-rate γ radiation enhances antioxidant activity. Here, we studied the ameliorative effect of continuous whole-body irradiation with low-dose-rate γ rays on diabetic nephropathy. Ten-week-old female db/db mice, an experimental model for type II diabetes, were irradiated with low-dose-rate γ rays from 10 weeks of age throughout their lives. Nephropathy was studied by histological observation and biochemical analysis of serum and urine. Antioxidant activities in kidneys were determined biochemically. Continuous low-dose-rate γ radiation significantly increases life span in db/db mice. Three of 24 irradiated mice were free of glucosuria after 80 weeks of irradiation. Histological studies of kidney suggest that low-dose irradiation increases the number of normal capillaries in glomeruli. Antioxidant activities of superoxide dismutase, catalase and glutathione are significantly increased in kidneys of irradiated db/db mice. Continuous low-dose-rate γ irradiation ameliorates diabetic nephropathy and increases life span in db/db mice through the activation of renal antioxidants. These findings have noteworthy implications for radiation risk estimation of non-cancer diseases as well as for the clinical application of low-dose-rate γ radiation for diabetes treatment.

摘要

有人提出,糖尿病肾病的发展在很大程度上是由氧化应激引起的。我们之前曾表明,持续暴露于低剂量率γ射线会增强抗氧化活性。在这里,我们研究了低剂量率γ射线全身连续照射对糖尿病肾病的改善作用。10 周龄的雌性 db/db 小鼠是 II 型糖尿病的实验模型,从 10 周龄开始接受低剂量率 γ 射线照射,直至其生命结束。通过对血清和尿液的组织学观察和生化分析来研究肾病。通过生化方法测定肾脏中的抗氧化活性。连续低剂量率γ射线照射可显著延长 db/db 小鼠的寿命。在 80 周的照射后,24 只照射的小鼠中有 3 只不再出现糖尿。肾脏的组织学研究表明,低剂量照射会增加肾小球中正常毛细血管的数量。照射的 db/db 小鼠肾脏中的超氧化物歧化酶、过氧化氢酶和谷胱甘肽的抗氧化活性显著增加。连续低剂量率γ 射线照射通过激活肾脏抗氧化剂,改善了 db/db 小鼠的糖尿病肾病并延长了其寿命。这些发现对非癌症疾病的辐射风险评估以及低剂量率γ 射线治疗糖尿病的临床应用具有重要意义。

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