促甲状腺激素（TSH）对心脏舒缩功能影响的研究

甲状腺功能减退（HT）和亚临床甲状腺功能减退（SCH）患者均可发生心脏舒缩功能障碍。而在SCH中仅有促甲状腺素（TSH）升高，甲状腺素水平正常，推测TSH在心脏舒缩功能障碍发生中可能发挥一定的作用。 甲状腺外的许多组织及细胞都存在TSH受体，TSH可通过受体结合在这些组织细胞发挥病理生理作用。本课题组的前期研究表明TSH在肝脏,内皮和平滑肌细胞上发挥一定作用。目前已有证据表明心肌细胞上也存在TSH受体表达。 本课题拟通过培养心肌细胞、完全摘除大鼠甲状腺等方法建立甲减动物模型，研究TSH对心肌细胞、心肌组织相关舒缩蛋白活性及表达、心脏舒缩功能的影响，以及对HT患者心脏舒缩功能的临床研究，探讨TSH对心脏舒缩功能影响的作用及机制。 因此，本课题是我们前期研究的拓展和深入，是对TSH的甲状腺外作用进一步研究，是对HT，尤其是SCH患者出现心脏舒缩功能障碍、引起心血管疾病发生发展机制的进一步探讨。

Cardiac systolic and diastolic dysfunction can occur on patients with hypothyroidism (HT)and subclinical hypothyroidism (SCH). SCH is characterized by increased serum TSH concentration in the presence of normal levels of serum T4 and T3. It assumes that TSH plays roles in cardiac systolic and diastolic dysfunction. It is well known that TSH receptor(TSHR)exists in a variety of extrathyroidal tissues and cells. In addition, many evidences have emerged to describe the pathophysiological actions of TSHR in those various tissues. Our previous studies have demonstrated that the liver, endothelial and smooth muscle cells expressed TSHR protein. Most importantly,the presence of TSHR have been documented in cardiac myocytes. The aim of the present study is to investigate the effects of TSH on protein activity and expression in cardiac tissue and myocytes,as well as the function of cardiac systolic and diastolic. By culturing cardiac myocytes and establishing animal models of hypothyroidism, clinical researches can be conducted to find the changes of cardiac systolic and diastolic dysfunction in patients with TH and SCH, and the roles of serum TSH levels on cardiac systolic and diastolic function. Therefore, this project is the expanding and deepening of previous studies. This study may explore the effects of TSH on extrathyroidal tissues and cells. Besides,it can be a futher discussion about the mechanisms of the occurrence and development of cardiovascular disease caused by HT and SCH patiens with cardiac systolic or diastolic dysfunction.