长QT综合征（LQTs）是致死率极高的恶性室性心律失常，常用临床治疗方式不能完全预防晕厥或猝死。课题组在对15例LQT患者的基因筛查的基础上发现两个LQT2突变，KCNH2-W927X和KCNH2-W410R。预实验证明KCNH2-W927X突变可导致Ikr电流密度明显下降，从而导致LQT2；而KCNH2-W410R突变迄今为止尚未见报道，位于HERG钾通道的S1跨膜区。稳心颗粒为一被证明对离子通道有明显干预作用的中成药，已被广泛用于临床，然而上尚未应用于LQTs的治疗。本研究拟在已经成功构建正常人诱导多能分化干细胞分化的心肌细胞（iPSC-CM）模型的基础上，从经典细胞电生理途径（CHO细胞模型）和iPSC-CM途径对W410R和W927X突变致LQTs的机制进行研究；并分别用稳心颗粒进行干预，研究稳心颗粒对KCNH2所编码HERG钾通道的功能影响，从而探讨其对LQT2的治疗作用。

Although the mortality of long QT syndrome (LQTs) is high, the traditional therapies could not prevent syncope or sudden cardiac death. We found two LQT2 mutations from 15 LQTs patients, KCNH2-W927X and KCNH2-W410R. KCNH2-W927X mutation was proved to lead to Ikr current decreased, and the latter has not been reported so far. KCNH2-W410R was a missense mutation, located at S1 section of HERG potassium channel, with Tryptophan being replaced by Arginine. The W410R mutation was predicted to cause abnormal structure of HERG protein, which could lead to LQT2. As a kind of Chinese herb, Wenxin Keli (WXKL) has been proved to be able to influence the cardiac ion channels, but it has not been used to treat LQTs patients. Based on the successfully established cardiomyocyte model derived from induced pluripotent stem cells (iPSC-CM), this study is designed to investigate the mechanism of KCNH2-W410R mutation and KCNH2-W927X mutation leading to LQTs in CHO cell model and iPSC-CM model, and to examine the effect of WXKL on HERG potassium channel, then to test whether WXKL could treat LQTs.