Bossowski Artur, Czarnocka Barbara, Bardadin Krzysztof, Urban Mirosława, Niedziela Marek, Dadan Jacek
ll Klinika Chorób Dzieci AM w Białymstoku.
Pediatr Endocrinol Diabetes Metab. 2007;13(2):63-70.
Apoptosis one of the form of programmed cell death is a physiological occurrence, requisite to the correct function of every organism. This is an active process that proceeds with a participation of the cellular metabolism embracing the activation of genes and the synthesis of proteins. The signal to apoptosis can be started practically in every cell of our organism. Disturbances of the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of this study was to estimate the expression of proapoptotic (Bax, Bak) and antiapoptotic (Bcl-2, Bcl-XL) proteins in thyroid tissues from 12 patients with Graves' disease (GD), 10 with non-toxic nodular goitre (NTNG) and 10 with toxic nodular goitre (TNG). Criteria for qualification of Graves' patients: large goitre, ophthalmopathy, TRAb > 5 U/L, positive titre of anti-TPO and anti-TG antibodies and concentration of TSH <0.45 microIU/mL more the 2-3 months from onset of the disease. Detection of apoptotic proteins in thyroid follicular cells was performed by Western Blot. These analysis was confirmed by immunohistochemistry using monoclonal antibodies in DAB chromogene visuality and marked by Mayer's haematoxylin. Identification of antiapoptotic Bcl-2 and Bcl-XL molecules in the thyroid follicular cells revealed a higher expression of both proteins in patients with Graves' disease (+++; ++, respectively) in comparison to patients with NTNG (++/+; +) and TNG (++; +). The detection of proapoptotic molecules showed higher expression of Bak (++/+) and Bax (+) in Graves' thyroid tissues while Bax was in trace amount in NTNG (0/+) and TNG (0/+). We conclude that alteration in the expression of antiapoptotic and proapoptotic proteins on surface of thyroid follicular cells may play a role in the pathogenesis of thyroid autoimmune disorders. In addition, suppression of apoptosis in Graves' disease led to predominance for proliferation of thyroid follicular cells which is responsible for goitre formation.
凋亡是程序性细胞死亡的一种形式，是一种生理现象，对每个生物体的正常功能都是必需的。这是一个活跃的过程，在细胞代谢的参与下进行，包括基因激活和蛋白质合成。凋亡信号实际上可以在我们机体的每个细胞中启动。凋亡调节的紊乱是许多疾病发病机制的关键环节，包括自身免疫性甲状腺疾病。本研究的目的是评估12例格雷夫斯病（GD）患者、10例非毒性结节性甲状腺肿（NTNG）患者和10例毒性结节性甲状腺肿（TNG）患者甲状腺组织中促凋亡蛋白（Bax、Bak）和抗凋亡蛋白（Bcl-2、Bcl-XL）的表达。格雷夫斯病患者的入选标准：甲状腺肿大、眼病、TRAb>5 U/L、抗TPO和抗TG抗体滴度阳性以及疾病发作2-3个月以上时TSH浓度<0.45微国际单位/毫升。通过蛋白质免疫印迹法检测甲状腺滤泡细胞中的凋亡蛋白。这些分析通过免疫组织化学得到证实，使用单克隆抗体在DAB显色剂显色，并以迈耶苏木精染色。在甲状腺滤泡细胞中鉴定抗凋亡的Bcl-2和Bcl-XL分子发现，与NTNG患者（++/+；+）和TNG患者（++; +）相比，格雷夫斯病患者中这两种蛋白的表达更高（分别为+++；++）。促凋亡分子的检测显示，格雷夫斯病甲状腺组织中Bak（++/+)和Bax（+）的表达较高，而Bax在NTNG（0/+)和TNG（0/+)中含量微量。我们得出结论，甲状腺滤泡细胞表面抗凋亡和促凋亡蛋白表达的改变可能在甲状腺自身免疫性疾病的发病机制中起作用。此外，格雷夫斯病中凋亡的抑制导致甲状腺滤泡细胞增殖占优势，这是甲状腺肿形成的原因。
