Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya University, Nagoya, Japan.
J Immunotoxicol. 2010 Jul-Sep;7(3):165-73. doi: 10.3109/15476910903510806.
Continuous low-dose injection of d-galactose induces changes in mice that resemble accelerated aging. As such, these mice have been used as models to study mechanisms of aging. Here, we examined whether repeated (daily, for 60 days) subcutaneous injections (at 50 mg D-galactose/kg) into young adult (i.e., 2-month-old) mice induced changes in key immune system organs that were on par with those associated with aging. The results showed that galactose-treated mice develop histologic changes in their thymic cortical and medullary regions; immunohistochemical analysis revealed unorganized distributions of keratin-5 and keratin-8 proteins in the thymus of these hosts. These histological changes in the thymus of D-galactose-treated mice were also observed in the organs of aged (i.e., 24-month-old control mice); however, in this latter group, these changes were accompanied by a strong infiltration of adipose cells. Galactose-treated mice also evinced alterations within their splenic white and red pulp. Further, ultrastructural analyses of the thymus and spleen of the treated mice revealed increases in irregularly shaped lymphocytes bearing visible pyknosis. It was also seen that levels of autophagy within thymic epithelial cells were greatly decreased in the tissues of the galactose-treated mice, an outcome also seen in aged mice. Lastly, the level of memory T-lymphocytes and percentage of IgM-B220-B-lymphocytes in spleens of the galactose-treated mice were both increased (albeit insignificantly so) relative to values among splenocytes of age-matched control; however, these levels were not clearly as elevated as would be expected in "elderly" mice. Taken together, our results strongly suggest that d-galactose treatment can induce structural changes in the thymus and spleen, and some changes in organ-associated cell phenotypes, that are similar to several effects seen with aging. However, the fact that many endpoints do not appear to be truly reflective of what should be seen in immune system organs/cells of "elderly" mice now calls into question the appropriateness of the use of d-galactose (i.e., is it histologically/immunotoxicologically-proper?) to create age-mimicry in mice.
连续低剂量注射 D-半乳糖会导致小鼠发生类似于加速衰老的变化。因此，这些小鼠已被用作研究衰老机制的模型。在这里，我们检查了反复（每天一次，持续 60 天）向年轻成年（即 2 个月大）小鼠皮下注射（50mg D-半乳糖/千克）是否会引起关键免疫系统器官的变化，这些变化与衰老相关。结果表明，半乳糖处理的小鼠在胸腺皮质和髓质区域出现组织学变化；免疫组织化学分析显示，这些宿主的胸腺中角蛋白-5 和角蛋白-8 蛋白分布紊乱。在 D-半乳糖处理的小鼠的胸腺中也观察到这些组织学变化；然而，在后一组中，这些变化伴随着脂肪细胞的强烈浸润。半乳糖处理的小鼠的脾白髓和红髓也发生了变化。此外，对处理小鼠的胸腺和脾脏进行超微结构分析显示，具有可见固缩的形状不规则淋巴细胞增多。还发现，半乳糖处理小鼠的胸腺上皮细胞中的自噬水平大大降低，这一结果也见于老年小鼠。最后，与年龄匹配的对照组相比，半乳糖处理小鼠脾脏中的记忆性 T 淋巴细胞水平和 IgM-B220-B 淋巴细胞的百分比均增加（尽管增加不显著）；然而，这些水平并没有像“老年”小鼠中预期的那样明显升高。总之，我们的结果强烈表明，D-半乳糖处理可以诱导胸腺和脾脏的结构变化，以及一些与衰老相关的器官相关细胞表型的变化。然而，许多终点似乎并没有真正反映出“老年”小鼠免疫系统器官/细胞中应该看到的情况，这使得 D-半乳糖（即它在组织学/免疫毒理学上是否合适？）用于在小鼠中产生模拟衰老的效果的合理性受到质疑。
