目前认为心肌Ryanodine受体（RyR2）过度磷酸化导致肌浆网钙离子漏，破坏钙离子稳态，在心力衰竭发生发展中具有重要作用。我们前期研究发现甲状腺激素（TH）与β受体信号通路存在有益的交互作用，而既往有研究显示β受体信号通路可以调节RyR2磷酸化。据此我们推测TH能够通过降低RyR2磷酸化水平，维持钙稳态，改善心肌兴奋收缩耦联，从而降低心律失常、改善心脏功能。为验证此假说，我们构建缺血性心力衰竭大鼠模型，分离获取心衰心肌细胞，采用IonOptix和激光共聚焦显微镜检测TH对心衰心肌收缩功能、电生理和钙瞬变等影响，应用腺病毒转染心肌细胞方式进一步研究TH和RyR2的作用关系，并验证其磷酸化调节机制。本课题旨在揭示TH在心力衰竭中的心肌保护作用及维持钙稳态的调节机制，为心力衰竭的治疗提供新的视野并奠定理论基础。

Ryanodine receptor (RyR2) hyperphosphorylation and subsequent endo/sarcoplasmic reticulum diastolic Ca2+ leaks are considered as trigger for loss of calcium homeostasis, which holds a critical role in the development and progression of heart failure. Our previous study found that there was beneficial crosstalk between thyroid hormone (TH) signaling pathway and β-receptor signaling pathway in the treatment of ischemic heart failure. Some researchers reveal that β-receptor signaling can regulate RyR2 phosphorylation. Therefore, we assume that TH may improve myocardial excitation-contraction coupling and maintain calcium homeostasis via reducing RyR2 phosphorylation, subsequently reducing arrhythmia inducibility and enhancing cardiac function. To address this hypothesis, rat model of ischemic heart failure will be made. IonOptix and laser confocal microscope will be utilized to explore the effects of TH on contractility, electrophysiology and calcium transients in failing cardiomyocytes isolated from above rat model. Further investigation will be carried out to study the underlying mechanism and the impact of TH on RyR2 phosphorylation with adenovirus transfection of cardiomyocytes. PCR array will be used to examine the expression of calcium signal transduction relevant proteins. This project will advance insights into the cardioprotective activity mediated by TH and its regulatory mechanism in maintaining calcium homeostasis in ischemic heart failure, endorsing TH as a potential therapeutic approach to treat heart failure.