Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Endocrine Unit, University Hospital AOU Policlinico G. Martino, 98125, Messina, Italy.
J Endocrinol Invest. 2020 Sep;43(9):1337-1342. doi: 10.1007/s40618-020-01231-7. Epub 2020 Mar 30.
Advanced glycation end products (AGEs) are increased in conditions of oxidative stress and promote inflammation by interacting with their receptor RAGE on cell membrane. By contrast, the soluble receptor sRAGE exerts protective effects by competing with RAGE for ligand binding. AGEs/sRAGEs interaction is involved in the pathogenesis of several diseases related to oxidative stress. In the present study, we evaluated the AGEs/sRAGEs oxidative balance in Hashimoto' thyroiditis (HT).
We measured the levels of sRAGE, by ELISA, and AGEs, by spectrophotometric method, in the serum of 50 HT patients (5 M, 45 F; mean age 38.5 ± 12 years) and 50 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy.
Serum sRAGEs were significantly lower (median 424 vs 738 pg/ml; p = 0.001) and AGEs higher (205 vs 114 AU/g prot; p = 0.001) in HT patients compared to controls, and the two parameters were inversely correlated (p = 0.016). Accordingly, the AGEs/sRAGEs ratio was threefold higher in HT patients than controls (0.48 vs 0.15; p = 0.0001). In regression analysis models, serum TPO-Ab were the main predictors for AGEs and sRAGEs levels and AGEs/sRAGEs ratio (p < 0.0001), irrespective of TSH and/or FT4 values.
sRAGEs were decreased and AGEs increased, suggesting a dysregulation of AGE/sRAGEs-related oxidative homeostasis in HT patients, even when in euthyroid status. Autoimmunity per se seems to play an important role in AGEs/sRAGE imbalance, irrespective of thyroid function alterations.
在氧化应激条件下,晚期糖基化终产物(AGEs)增加,并通过与细胞膜上的受体 RAGE 相互作用促进炎症。相比之下,可溶性受体 sRAGE 通过与 RAGE 竞争配体结合发挥保护作用。AGEs/sRAGE 相互作用参与了几种与氧化应激相关疾病的发病机制。在本研究中,我们评估了桥本甲状腺炎(HT)中的 AGEs/sRAGEs 氧化平衡。
我们通过 ELISA 测量了 50 例 HT 患者(5 名男性,45 名女性;平均年龄 38.5±12 岁)和 50 名年龄、性别和 BMI 匹配的健康对照者血清中的 sRAGE 水平,并通过分光光度法测量了 AGEs 水平。所有受试者在招募时均为甲状腺功能正常,且均未接受 LT-4 治疗。
与对照组相比,HT 患者的血清 sRAGEs 明显降低(中位数 424 与 738 pg/ml;p=0.001),AGEs 水平升高(205 与 114 AU/g prot;p=0.001),且两者呈负相关(p=0.016)。因此,HT 患者的 AGEs/sRAGEs 比值比对照组高三倍(0.48 与 0.15;p=0.0001)。在回归分析模型中,血清 TPO-Ab 是 AGEs 和 sRAGEs 水平以及 AGEs/sRAGEs 比值的主要预测因子(p<0.0001),而与 TSH 和/或 FT4 无关。
sRAGEs 降低,AGEs 升高,提示 HT 患者的 AGE/sRAGEs 相关氧化平衡失调,即使在甲状腺功能正常的情况下也是如此。自身免疫本身似乎在 AGEs/sRAGE 失衡中起着重要作用,而与甲状腺功能改变无关。