TRAb对心肌肥厚的影响及其机制研究

Graves’病（Graves disease,GD）可引起严重的心功能障碍，尤以心肌肥厚最为突出。目前认为该病的发生机制为促甲状腺激素受体抗体（TRAb）结合于甲状腺细胞促甲状腺激素受体（TSHR），模拟促甲状腺激素（TSH）作用，致甲状腺素（TH）过度分泌导致。但有研究发现，Graves疾病中可出现TRAb与TH的非平行性升高，TRAb血清水平与心功能损伤成正相关，且课题组前期研究已证实心肌细胞表面TSHR的表达。由此我们推测，TRAb是否可能通过结合于心脏TSHR，激活一系列信号通路，调控相关蛋白及炎症因子表达，独立引起心肌肥厚？本课题拟通过建立TRAb阳性的细胞和动物模型，研究TRAb对心肌肥厚标志物、肥厚相关炎症因子及其通路分子表达的影响，初步明确TRAb在甲亢型心脏病中的独立致病作用及机制。本研究为Graves病诱发心肌肥厚发病机制的补充性探索。

GD can cause severe cardiac dysfunctions, and myocardial hypertrophy is the most obvious pathological change in one of them. Now that the pathogenesis of the disease is thyroid stimulating hormone receptor antibodies (TRAb) binding to thyroid stimulating hormone receptors (TSHR) of thyroid cells, simulate of thyroid stimulating hormone (TSH), lead to excessive secretion of thyroid hormone (TH). However, it has been found that TRAb dose not increase in parallel with TH, and the level of serum TRAb is positively correlated with the damaging of cardiac function, and the previous study of the research group has confirmed the expression of TSHRs on the surface of myocardial cells. Thus, we speculate that TRAbs may combine with cardiac TSHRs, activate a series of signaling pathways, regulate the expression of related proteins and inflammatory factors, result in cardiac hypertrophy independently? This research is exploring the expression of inflammatory cytokines and the related pathways of cardiac hypertrophy by the establishment of TRAb positive cells and animal model, initially identify the independent pathogenic role and mechanism of TRAb in hyperthyroid heart disease. The present study will be the supplementary exploration to the mechanism of Graves induced myocardial hypertrophy.