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单次低剂量全身照射对非肥胖糖尿病-H2h4小鼠自身免疫性甲状腺炎的加重作用。

Exacerbation of autoimmune thyroiditis by a single low dose of whole-body irradiation in non-obese diabetic-H2h4 mice.

作者信息

Nagayama Yuji, Kaminoda Kazuhisa, Mizutori Yumiko, Saitoh Ohki, Abiru Norio

机构信息

Department of Medical Gene Technology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

出版信息

Int J Radiat Biol. 2008 Sep;84(9):761-9. doi: 10.1080/09553000802345910.

Abstract

PURPOSE

To evaluate how irradiation affects thyroid autoimmunity in mouse models of Hashimoto's thyroiditis and Graves' hyperthyroidism.

MATERIALS AND METHODS

Non-obese diabetic (NOD)-H2(h4) mice spontaneously develop anti-thyroglobulin (Tg) antibodies and thyroiditis when supplied with sodium iodine (NaI) in the drinking water. BALB/c mice develop anti-thyrotropin receptor (TSHR) antibodies and hyperthyroidism following immunization with adenovirus expressing TSHR (Ad-TSHR). Mice were irradiated as follows: A single whole-body irradiation with 0.05, 0.5 or 3 Gy one week before or after the beginning of NaI or immunization with Ad-TSHR, fractionated whole-body irradiations with 0.05 Gy twice a week or 0.5 Gy once a week from one week before NaI or Ad-TSHR immunization, or a single regional irradiation to the thyroid gland with 0.5 Gy one week before NaI. The effect of a single irradiation with 0.05, 0.5 or 3 Gy on splenocytes was also evaluated.

RESULTS

A single whole-body irradiation with 0.5 Gy one week before NaI exacerbated thyroiditis and increased anti-Tg antibody titers in NOD-H2(h4) mice. In contrast, any irradiation protocols employed did not affect incidence of hyperthyroidism or anti-TSHR antibody titers in BALB/c mice. High-dose irradiation increased the relative ratios of effector T cells to regulatory T cells (an indication of enhanced immune status) but kills most of T cells.

CONCLUSIONS

These results indicate that a single whole-body low-dose irradiation with 0.5 Gy exacerbates thyroiditis in NOD-H2(h4) mice, data consistent with some clinical evidence for increased incidence of thyroid autoimmunity by environmental irradiation.

摘要

目的

评估辐射如何影响桥本甲状腺炎和格雷夫斯甲亢小鼠模型中的甲状腺自身免疫。

材料与方法

非肥胖糖尿病(NOD)-H2(h4)小鼠在饮用水中添加碘化钠(NaI)时会自发产生抗甲状腺球蛋白(Tg)抗体和甲状腺炎。BALB/c小鼠在用表达促甲状腺激素受体(TSHR)的腺病毒(Ad-TSHR)免疫后会产生抗促甲状腺激素受体抗体和甲亢。小鼠接受如下照射:在开始给予NaI或用Ad-TSHR免疫之前或之后一周进行一次0.05、0.5或3 Gy的全身照射,从给予NaI或Ad-TSHR免疫前一周开始每周两次0.05 Gy或每周一次0.5 Gy的分次全身照射,或者在给予NaI前一周对甲状腺进行一次0.5 Gy的局部照射。还评估了一次0.05、0.5或3 Gy照射对脾细胞的影响。

结果

在给予NaI前一周进行一次0.5 Gy的全身照射会加重NOD-H2(h4)小鼠的甲状腺炎并提高抗Tg抗体滴度。相比之下,所采用的任何照射方案均未影响BALB/c小鼠甲亢的发生率或抗TSHR抗体滴度。高剂量照射增加了效应T细胞与调节性T细胞的相对比例(表明免疫状态增强),但会杀死大多数T细胞。

结论

这些结果表明一次0.5 Gy的全身低剂量照射会加重NOD-H2(h4)小鼠的甲状腺炎,这一数据与环境辐射导致甲状腺自身免疫发生率增加的一些临床证据一致。

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