甲状腺功能减退（甲减）和亚临床甲状腺功能减退（SCH）患者常合并心脏功能紊乱。过去认为甲减患者的心功能改变是甲状腺激素水平降低所致，而忽视了促甲状腺素（TSH）的作用。我们前期研究中选用了细胞模型（TSH刺激大鼠心肌细胞H9C2）以及动物模型（甲减及SCH小鼠模型）来研究TSH对心功能的调控作用。我们在上述细胞模型及动物模型的心室中发现miR-1的表达随着TSH水平的升高而显著增加。此外，超极化激活的环核苷酸门控通道2（HCN2）是miR-1在心肌细胞中的潜在靶基因。心肌细胞过表达miR-1后，HCN2表达显著降低；心肌细胞抑制miR-1表达后，HCN2表达显著增加。基于前期研究，我们的课题将进一步研究TSH对miR-1及其下游靶点HCN2的调控机制，并将以miR-1/HCN2为切入点，深入探讨TSH诱发心功能紊乱的分子机制，为甲减性心脏病以及SCH合并心脏病的防治提供新线索和理论依据。

Hypothyroidism and subclinical hypothyroidism (SCH) are usually accompanied by cardiac systolic and diastolic dysfunction. It was previously considered that cardiac dysfunction in patients with hypothyroidism was induced by the decrease of thyroid hormone level, however, the role of thyroid stimulating hormone (TSH) remains largely unclear. In our study, we found the miR-1 expression was upregulated in H9C2 cells stimulated by TSH in vitro and in the ventricular tissues of hypothyroidism mouse and SCH mouse models. We also found hyperpolarization-activated cyclic nucleotide-gated channel (HCN2) was a potential target of miR-1 in cardiomyocytes. HCN2 was down-regulated when miR-1 was overexpressed in H9C2 cells, whereas HCN2 expression was significantly increased when miR-1 was inhibited in H9C2 cells. Based on these findings, we plan to explore the molecular mechanism underlying the regulation of TSH in miR-1 expression and its target HCN2 in cardiomyocytes, and the potential effect of miR-1/HCN2 in cardiac dysfunction induced by TSH, thus providing novel clues for preventing and treating hypothyroidism and SCH-related heart diseases.