心功能障碍是脓毒症患者死亡的重要原因，抑制caspase-3的活化和心肌细胞凋亡对改善脓毒症患者的心功能具有重要意义，然而脓毒症时心肌细胞凋亡发生的机制并不完全清楚。虽然已证实儿茶酚胺参与了慢性心力衰竭和心肌缺血时心肌细胞凋亡的发生机制，但它在脓毒症心肌细胞凋亡发生中有何作用尚缺乏研究。我们前期研究发现，耗竭心脏去甲肾上腺素（NE）几乎能完全抑制内毒素诱导的小鼠心肌细胞凋亡,但其机制尚不明了。因此，本研究利用脓毒症大鼠模型和培养的心肌细胞，从PKA、CaMK II、NF-kappa B、MAPK信号和细胞凋亡通路,阐明NE参与脓毒症心肌细胞凋亡发生的分子机制，并利用不同的肾上腺素能受体激动剂和阻断剂，探讨不同肾上腺素能受体在脓毒症心肌细胞凋亡发生中的调节作用，对进一步阐明脓毒症心肌细胞凋亡的发生机制、寻找脓毒症心功能障碍的治疗靶点和指导临床合理使用血管活性药物具有重要的科学价值。

It is very important to prevent myocardial depression for improving survival in septic patients. Capase-3 activation and cardiomyocyte apoptosis play an important role in myocardial depression during sepsis, but the mechanisms for this kind of cardiomyocyte apoptosis is not fully understood. Although it is well known that catecholamine involves cardiomyocyte apoptosis in chronic heart failure and myocardial ischemia, the contributory role of catecholamine to the development of cardiomyocyte apoptosis during severe sepsis has not yet been investigated. We recently found that reserpine that exhausted cardiac norepinephrine (NE) without markedly decreasing plasma NE level almost completely inhibited lipopolysaccharide (LPS)-induced myocardial apoptosis, but the molecular mechanism for this phenomenon is unclear. Therefore, the present study is designed to investigate the molecular mechanisms by which NE mediates sepsis-induced cardiomyocyte apoptosis via examining myocardial PKA, CaMK II, NF-kappaB and MAPK signal pathways as well as apoptotic signaling pathways in septic animals and cytokine-treated adult rat cardiomyocytes, and to determine the regulatory role of different adrenergic receptors (AR) in the development of cardiomyocyte apoptosis during sepsis by using AR agonists or antagonists. These investigations will further explain the molecular mechanisms for sepsis-triggered cardiomyocyte apoptosis, help identify the therapeutic target for septic cardiac dysfunction, and provide the evidence for reasonable selection of vasoactive drugs in the treatment of severe sepsis.