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目的观察NOD.H-2h4小鼠自身免疫性甲状腺炎时甲状腺内细胞凋亡和凋亡相关蛋白Fas、Fas-L和FLIP的表达情况,研究细胞凋亡在自身免疫性甲状腺炎中的作用。方法7~8周龄的NOD.H-2h4小鼠,饲以0.05%NaI溶液作为实验组,对照组小鼠则饲以自来水。在给碘后8,16,32周处死小鼠,HE染色观察甲状腺的炎症程度,TUNEL方法观察甲状腺内细胞凋亡情况,免疫组化方法观察凋亡相关蛋白Fas、Fas配体(Fas-L)和FLICE抑制蛋白(FLIP)的表达情况。结果实验组小鼠出现自身免疫性甲状腺炎,对照组无甲状腺炎产生。甲状腺炎时,TUNEL染色阳性细胞主要集中在浸润淋巴细胞中,甲状腺滤泡上皮细胞罕见凋亡;Fas、Fas-L和FLIP主要表达在甲状腺内的浸润淋巴细胞上;部分甲状腺滤泡上皮细胞表达Fas,而Fas-L和FLIP在甲状腺滤泡上皮细胞未见明显表达。结论NOD.H-2h4小鼠自身免疫性甲状腺炎时甲状腺细胞无明显凋亡,提示细胞凋亡机制未参与甲状腺炎的发病。甲状腺内浸润淋巴细胞虽然表达Fas但并未出现明显凋亡,这可能与其同时表达抗凋亡蛋白FLIP有关。
Objective To investigate the expression of apoptosis-related proteins Fas, Fas-L and FLIP in thyroid during autoimmune thyroiditis in NOD.H-2h4 mice and the role of apoptosis in autoimmune thyroiditis. Methods NOD.H-2h4 mice aged 7-8 weeks were fed with 0.05% NaI solution as experimental group, and control mice were fed with tap water. Mice were sacrificed at 8, 16 and 32 weeks after iodine treatment, the degree of inflammation of the thyroid gland was observed by HE staining, the apoptosis of thyroid gland was observed by TUNEL method, and the expression of Fas-Ligand (Fas-L) ) And FLICE inhibition protein (FLIP) expression. Results In experimental group, autoimmune thyroiditis occurred in mice and no thyroiditis occurred in control group. Thyroiditis, TUNEL staining positive cells mainly in infiltrating lymphocytes, thyroid follicular epithelial cells rare apoptosis; Fas, Fas-L and FLIP mainly in infiltrating lymphocytes in the thyroid; part of thyroid follicular epithelial cells Fas, but no significant expression of Fas-L and FLIP in thyroid follicular epithelial cells. Conclusion NOD.H-2h4 mice with autoimmune thyroiditis no significant apoptosis of thyroid cells, suggesting that apoptosis is not involved in the pathogenesis of thyroiditis. Thyroid infiltration of lymphocytes, although the expression of Fas but did not show significant apoptosis, which may be related to its expression of the anti-apoptotic protein FLIP.