大量证据表明肝硬化易导致患者左心功能受损，从而引发肝硬化心肌病(CCM)。研究显示心肌细胞β1-AR功能受损及心肌细胞凋亡在CCM发病机制中起关键作用，肝硬化患者GRK5过表达。我们前期研究发现CCM动物模型心肌细胞病理损伤与超声评估的心功能减弱相关，且存在心肌细胞β1-AR功能减低、细胞凋亡加剧。因此假设：肝硬化患者GRK5表达上调，及β1-AR介导的CaMKⅡ通路激活，是引发CCM的重要机制；超声评估的CCM心肌应变及心功能改变，与活化的CaMKⅡ、GRK5水平相关联。本课题拟利用CCM模型，研究β1AR-Gs-Ca2+-CaMKⅡ通路关键因子及GRK5表达水平对肝硬化心肌细胞的损伤作用，并基于3D-STI及小动物超声技术建立超声评估的心功能与CaMKⅡ、GRK5表达水平的关联。本研究将不仅阐明CCM致病机制，也为超声联合特异性生化指标早期诊断CCM并实现其靶向治疗提供新的标准与方法。

A large number of evidences have shown that liver cirrhosis can easily lead to the impairment of left heart function, that is CCM. It is believed that β1-AR density, function impairment and cardiomyocyte apoptosis play an important role in the pathogenesis of CCM. Recently, we found that the pathological damage of cardiac cells in CCM animal model was correlated with the decrease of cardiac function assessed by ultrasound, and there were decreased β1-AR function, up-regulated apoptosis and over expression of GRK5 in cardiac cells. Therefore, we hypothesized that the up-regulation of GRK5 expression and β1-AR mediated activation of CaMKⅡ pathway in patients with liver cirrhosis are important mechanisms for CCM; the changes of cardiac strain and cardiac function in CCM assessed by ultrasound are correlated with the levels of activated CaMKⅡ and GRK5. The purpose of this study is to study the effects of the main members of β1AR-Gs-Ca2+-CaMKⅡ pathway and the expression level of GRK5 on the injury of cirrhotic cardiomyocytes through CCM model, and to establish the correlation between the cardiac function assessed by ultrasound and the expression level of GRK5 and CaMKⅡ based on 3D-STI and ultrasound imaging of small animal technology. This study will not only clarify the pathogenesis of CCM, but also provide a new standard and method for early diagnosis and targeted treatment of CCM by ultrasound combined with specific biochemical indicators.