急性甲亢肌病（ATM）是甲亢较少见的严重并发症，存在不同程度的脑水肿或脑出血，表现为急性延髓麻痹，病情变化迅速、危及生命，目前的治疗策略为应用抗甲状腺药物和糖皮质激素，可迅速缓解症状。ATM具体发病机制尚不明确。本课题组的前期研究发现，发生ATM患者存在高水平的血浆促甲状腺激素受体抗体（TRAb），且甲亢患者血浆中血管舒张因子均增加，推测可能与过高的TRAb结合促甲状腺激素受体（TSHR）后对下游通路的影响有关。本课题拟在分子、细胞及动物层次，从脑血管内皮细胞的舒缩功能、炎症反应、氧化应激等多个角度出发，研究TRAb对脑血管内皮细胞功能的影响，同时应用蛋白质组学及转录组学整合研究策略，筛选并验证由TRAb导致的Graves病小鼠延髓及脑脊液的差异分子，为进一步探讨ATM及其延髓麻痹的机制、以及糖皮质激素的干预研究提供新的理论依据和实验基础。

Acute thyrotoxic myopathy (ATM) is a rare but serious complication of hyperthyroidism. It includes different degrees of encephaledema or cerebral hemorrhage with obscure pathogenesis, presenting as abrupt onset of bulbar palsy. The conditions could deteriorate rapidly with attendant morbidity. Currently with treatment as ATD and glucocorticoid, most patients can get a complete recovery. However, the specific mechanism of ATM is still not understood. In the previous data of our group, we found that patients with ATM were prone to have a relatively high levels of thyrotrophin receptor antibody (TRAb) and patients of hyperthyrotism had higher levels of blood endothelium-derived relaxing factor. These findings are support of our hypothesis that the excess of TRAb may influence the function of vascular endothelial cell (VEC) through influencing TSHR-related pathway. Therefore, in this study we are focusing on the influence of TRAb on the penetration function, inflammatory response, and oxidative stress of VEC in levels of molecule, cell and animal model. At the same time, we will combine application of proteomics and transcriptomics to explore distinction of medulla and cerebrospinal fluid between TRAb (+) and TRAb (-) rats in mRNA and protein levels to search for potential targeted factors. This research is important and valuable for further exploring of the pathogenesis of acute thyrotoxic bulbar palsy in ATM, and also shed light on the functional mechanism of glucocorticoid’ intervening role.