心功能障碍是脓毒症患者死亡的重要原因，但其机制尚未明了，目前缺乏有效治疗措施。业已证明，心脏儿茶酚胺（CA）参与了脓毒症心肌损伤的发生机制；而且，心脏内源性肾上腺素能(ICA)细胞可以释放CA，这种CA调节心脏发育和缺血性心肌损伤。然而，ICA细胞来源的CA在脓毒症心肌损伤中有何作用？尚不清楚。我们发现脂多糖(LPS)能促进ICA细胞释放CA，这种CA可促进LPS刺激的心肌细胞释放TNF-α，但LPS促进ICA细胞释放CA的机制并不清楚。因此，本项目利用培养的ICA细胞、乳鼠和成年鼠心肌细胞以及乳鼠和成年鼠脓毒症心肌损伤模型，从TLR4与肾上腺素能受体信号通路、心肌炎症、能量代谢和心脏发育的角度，探讨LPS促进ICA细胞释放CA的机制及其在脓毒症心肌损伤中的作用，对进一步阐明脓毒症心肌损伤的机制，特别是新生儿脓毒症对心脏发育和心肌的作用机制，以及寻找新的脓毒症心肌病的治疗策略具有重要意义。

Cardiac dysfunction is a leading cause of mortality in septic patients, but its mechanism has not been fully understood and no specific therapy exists. It has been demonstrated that cardiac catecholamine is involved in the pathogenesis of sepsis-induced myocardial injury, the intrinsic cardiac adrenergic (ICA) cells synthesize catecholamines, and the released catecholamines from ICA cells can regulate cardiac development and ischemia-induced myocardial injury. However, it is unclear whether catecholamines from ICA cells contribute to sepsis-induced myocardial injury. Our preliminary study observed that lipopolysaccharide (LPS) increased catecholamine synthesis and release in ICA cells, which promoted tumor necrosis factor-alpha (TNF-alpha) production in LPS-challenged cardiomyocytes, but the mechanisms responsible for the increased catecholamine release from ICA cells by LPS needs to be identified. Therefore, the aim of the present study is to investigate the molecular mechanisms for increased catecholamines release from ICA cells by LPS and to identify the role of catecholamines released from ICA cells in sepsis-induced neonatal and adult myocardial injury, via analysis of TLR4 and adrenoceptor-associated signal pathways, myocardial inflammation and energy metabolisms as well as cardiac development, by using cultured ICA cells, neonatal and adult rat cardiomyocytes as well as the neonatal and adult rat models of sepsis-induced myocardial injury. These investigations will further explain the molecular mechanisms for sepsis-triggered myocardial injury, especially for the effect of neonatal sepsis on cardiac development and myocardium, and help to find new therapeutic strategies for the treatment of sepsis cardiomyopathy.