凋亡相关因子参与自身免疫性甲状腺疾病发病的研究

目的:了解细胞凋亡相关蛋白Fas,FasL和Bcl-2表达在自身免疫性甲状腺疾病发病机制及病理变化中的作用及意义。方法:采用免疫组织化学方法,检测20例桥本甲状腺炎,20例Graves病以及20例甲状腺腺瘤(作为对照组)患者甲状腺标本中Fas、FasL和Bcl-2表达及分布。结果:Fas在所有的标本中表达,主要分布于甲状腺滤泡细胞表面和细胞质上。除3例甲状腺瘤标本外,其余均表达FasL。Bcl-2表达于15例桥本甲状腺炎、19例Graves病以及17例甲状腺瘤滤泡细胞上。在甲状腺瘤滤泡细胞上表达中等强度Fas,很少或是没有表达FasL。在桥本甲状腺炎中Fas和FasL免疫染色强阳性甲状腺滤泡细胞多分布于浸润淋巴滤泡附近,浸润淋巴细胞中Fas、FasL免疫染色相对较弱。在Graves病中,Fas表达强度与桥本甲状腺炎类似,但FasL表达却更弱。在Graves病和甲状腺瘤组织中,Bcl-2表达两者类似。但在桥本甲状腺炎组织中,分布于浸润淋巴细胞附近的甲状腺滤泡细胞以及生发中心的淋巴细胞上,Bcl-2表达很弱。结论:Fas、FasL和Bcl-2表达在桥本甲状腺炎和Graves病中相似。FasL高表达和Bcl-2低表达可能引起桥本甲状腺炎滤泡细胞凋亡。进一步证明3种凋亡相关因子在自身免疫性甲状腺疾病发病机制中的作用。在桥本甲状腺炎中,滤泡细胞凋亡并非由浸润淋巴细胞其FasL发挥作用直接杀伤,但是它们能分泌细胞因子促进滤泡细胞自身Fas、FasL表达,从而导致滤泡细胞凋亡。

The function of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disorders

AIM: To investigate the expression and function of apoptosis-related protein, Fas, FasL, and Bcl-2 in the pathogenesis of autoimmune thyroiditis. METHODS: Immunohistochemical staining was performed on 20 Hashimoto's thyroiditis (HT), 20 Graves' disease (GD), and 20 thyroid follicular adenoma (TFA, as control).RESULTS: All the cases expressed Fas, mainly on the cell surface and cytoplasm. FasL was found in all except 3 of the TFA. Bcl-2 in 15 of HT, 19 of GD, 17 of TFA. In TFA follicular cells expressed moderate Fas and minimal or absent FasL. In HT, follicles adjacent to infiltrating lymphocytes showed a increased levels of Fas and FasL, but infiltrating lymphocytes exhibited weaker staining of Fas and FasL than thyrocytes. In GD, thyrocytes and lymphocytes showed nearly similar Fas with HT, but rather weaker for FasL than HT. Bcl-2 was nearly similar in GD and TFA, but follicular cells in vicinity of lymphocytes and lymphocytes located in germinal centers of HT tissues exhibited significantly weaker. CONCLUSION: The expression of Fas, FasL and Bcl-2 in Hashimoto's thyroiditis and Graves' disease was nearly similar. Strong FasL expression and weak Bcl-2 expression on the follicles in HT may induce apoptosis. These results provide further proof that the functions of Fas and its ligand and Bcl-2 may play an important part in the pathogenesis of autoimmune thyroid diseases. The lymphocytes do not seem to be directly engaged in the process with their own FasL, but they may provide some cytokines that , in turn , up-regulates Fas and/or FasL leading to apoptosis.