Contempre B, Le Moine O, Dumont J E, Denef J F, Many M C
Institute of Interdisciplinary Research (IRIBHN), Free University of Brussels, Medicine Faculty, Belgium.
Mol Cell Endocrinol. 1996 Nov 29;124(1-2):7-15. doi: 10.1016/s0303-7207(96)03921-4.
Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role.
硒缺乏引起的自由基损伤和纤维化被认为与黏液性水肿型克汀病的发病机制有关。迄今为止，尚无途径能解释硒缺乏与组织纤维化之间的联系。药理剂量的碘会导致缺碘甲状腺发生坏死。如果腺体同时也缺乏硒，坏死会显著增加，进而发展为纤维化。我们复制了这个大鼠模型来探究硒缺乏在组织修复缺陷中的作用。起初，缺硒组和对照组上皮细胞和成纤维细胞的增殖指数相当。然后，在缺硒的甲状腺中，炎症反应更为明显，主要由巨噬细胞组成。上皮细胞的增殖指数下降，而成纤维细胞的增殖指数增加。这些甲状腺发展为纤维化。在缺硒大鼠的巨噬细胞中，TGF-β免疫染色显著。抗TGF-β抗体恢复了增殖指数，并阻止了向纤维化的发展。在硒缺乏时，甲状腺会发生活跃的纤维化过程，其中炎症反应和过量的TGF-β起关键作用。
