从初级纤毛调控甲状腺球蛋白合成分解途径探讨化痰散结法治疗Graves病的作用机制

Graves病（GD）是以甲状腺肿大和功能亢进为特征的器官特异性自身免疫性疾病，抗甲状腺药物停药后复发率高是当前影响GD治疗的瓶颈，其中甲状腺肿大为其关键高风险因素。初级纤毛（PC）是细胞膜表面高度分化的结构，介导细胞内外信号的转导。近两年研究发现，PC结构和功能紊乱可导致GD，其发育受免疫失衡影响。同时发现定位于PC的Taar1是调控Tg合成分解的关键因子。“免疫—PC—Tg”可能是GD发病的新途径。GD属中医“瘿病”范畴，化痰散结法为基本治法。我们前期研究发现化痰散结法显著改善甲状腺肿大，下调Tg表达，并调节免疫失衡，其深层作用靶点可能与上述PC途径相关。本研究拟通过体内和体外实验，采用扫描电镜、激光共聚焦、基因沉默及相关分子生物学技术，重点探讨并验证化痰散结法通过PC调控Tg合成分解治疗GD的作用机制，是既往研究的延伸，以期为中医药治疗GD提供依据，为提高GD综合疗效提供思路。

Graves disease（GD）is an organ-specific autoimmune disease characterized by goiter and Hyperthyroidism. The high recurrence rate after the withdrawal of antithyroid drugs limits the overall therapeutic effect of GD and Goiter is a key high risk factor。Primary cilia (PC) is a highly differentiated structure on the surface of the cell membrane, which mediates the signal transduction of the cell. In the past two years, research found GD can be caused by abnormal structure and function of PC which is also affected by immune disorder. Taar1 located at PC can regulate the synthesis and degradation of Tg. It will be a new way to explore the mechanism of GD. GD belongs to the category of gall disease in TCM, and the mode of resolving phlegm and dissipating stagnation is the basic treatment. in the past, it has been proved that the mode of resolving phlegm and dissipating stagnation can significantly reduce goiter, down-regulate the expression of Tg and regulate immune disorder. Is it related to the above-mentioned PC pathway? Through experiments in vivo and in vitro, we will focuse on the mechanism of the mode of resolving phlegm and dissipating stagnation in regulating Tg synthesis and degradation of GD through PC by using scanning electron microscope, laser confocal, gene silencing and other molecular biology techniques, which is an extension of previous studies. This study would provide a basis for traditional Chinese medicine in the treatment of GD and ideas for improving the comprehensive efficacy of GD.