脓毒症(sepsis)所致心肌抑制患者病死率可高达70～90%，目前临床上尚无特别有效的治疗办法。在脓毒症心肌抑制的病理生理机制中炎症和交感肾上腺素能神经系统持续过度激活扮演了重要角色。PKI是心脏中表达的一种特异性抑制PKA的热稳定多肽，心脏中PKI对脓毒症所致心肌抑制有何作用？至今尚未见报道。我们发现在心肌细胞特异性过表达PKI（PKI-GFP）抑制PKA激活能够显著延长LPS诱导的脓毒症小鼠的存活时间，并增强其心功能。进一步研究发现心肌细胞特异性过表达PKI抑制PKA激活能减少脓毒症小鼠心肌细胞的凋亡和纤维化，减轻LPS诱导的心肌炎症细胞浸润。因此，我们推测心肌细胞PKA抑制保护脓毒症预后可能与其能够减轻心肌炎症有关。因此，本项目拟围绕1）心肌细胞PKA抑制是否能保护脓毒症预后？其机制是否与其减轻心肌炎症有关？2）脓毒症时，心肌细胞PKA抑制是如何减轻心肌炎症的？其信号通路如何？

The mortality of cardiac dysfunction caused by sepsis can be as high as 70 - 90%，, and there is no special effective treatment in clinic. Sympathetic overactivity and inflammation play the important roles in the pathophysiological process of cardiac dysfunction during sepsis. PKI is a thermal stable polypeptide expressed in the heart, which is a specific protein to inhibit the activation of PKA. The effect of PKI on cardiac arrest caused by sepsis in the heart has not yet been reported. Our preliminary experimental data showed that inhibition of PKA by overexpression of PKI-GFP in cardiomyocytes could prolong survival time, and enhance cardiac function in LPS-induced septic mice. Further studies showed that the specific overexpression of PKI-GFP in cardiomyocytes also could reduce the apoptosis of cardiomyocytes, inhibit myocardial fibrosis and alleviate inflammatory infiltration in myocardium of septic mice. Therefore, we speculate that the beneficial effect of PKA inhibition in cardiac myocytes may be associated with the reduction of myocardial inflammation in septic mice. This project aimed to study: 1) Does the PKA inhibition in cardiac myocytes can benefit the prognosis of sepsis? Whether the protective effect on sepsis by PKA inhibition in cardiac myocytes is related to the reduction of myocardial inflammation in septic mice? 2) How does PKA inhibit in cardiac myocytes produce the anti-inflammatory effect in the myocardium? What is the signal pathway?