革兰氏阳性细菌所致脓毒症心肌损伤表型特征及机制研究

The core mechanism of sepsis is unbalanced body inflammatory response that is caused by infection. Bacterial infection remains the primary cause of sepsis. However, only 40% to 60% of sepsis caused by gram-negative bacterial infection, and the incidence of sepsis caused by gram-positive bacteria increased year by year. Whatever animal model or clinical experiment, gram-positive bacteria release exotoxin, which is different from the release of endotoxin of gram-negative bacteria. Data showed about 40% to 50% of patients with sepsis can have myocardial injury. Our previous study found that patients with sepsis caused by gram-positive bacteria were more likely to have circulatory system dysfunction or failure. Based on gram-positive bacteria and gram-negative bacteria release toxin / endotoxins that may cause the difference process of severe infection, this program through make gram-positive bacteria and gram-negative bacteria infected sepsis rat model respectively by heat-inactivated Staphylococcus aureus and heat-inactivated Escherichia coli intraperitoneal injection, in order to evaluation the phenotypic characteristics of sepsis myocardial injury caused by gram-positive bacteria infected. Although, from the direct effect of toxin on myocardial, extent of myocardial cell apoptosis and myocardial cell energy metabolism three aspects, to explore the possible mechanisms of sepsis myocardial injury caused by gram-positive bacteria infected. It is could be provide a new idea to realize the early identification and accurate treatment of sepsis myocardial injury.

脓毒症是由感染导致的机体失控的炎症反应。细菌感染依然是脓毒症诱发的首要病因，然细菌所致脓毒症中仅40%-60%为革兰氏阴性细菌感染，革兰氏阳性细菌所致脓毒症发病率逐年升高。革兰氏阳性细菌释放外毒素，在动物模型和临床环境中均与革兰氏阴性细菌释放内毒素有所区别。另有数据表明，40%-50%脓毒症患者可出现心肌损伤。本课题组前期研究发现革兰氏阳性主要致病菌所致脓毒症患者更易发生循环系统功能障碍或衰竭。基于革兰氏阳性细菌及革兰氏阴性细菌释放外毒素/内毒素在致机体严重感染过程中可能存在的差异，本课题通过分别热灭活金黄色葡萄球菌及热灭活大肠埃希菌腹腔注射构建革兰氏阳性细菌脓毒症及革兰氏阴性细菌脓毒症大鼠模型，评价革兰氏阳性细菌所致脓毒症心肌损伤的表型特征，从毒素对心肌的直接作用、心肌细胞凋亡以及心肌细胞能量代谢三个方面，探讨革兰氏阳性细菌致脓毒症心肌损伤的可能机制。

脓毒症是由感染导致的机体失控的炎症反应。细菌感染依然是脓毒症诱发的首要病因，然细菌所致脓毒症中仅40%-60%为革兰氏阴性细菌感染，革兰氏阳性细菌所致脓毒症发病率逐年升高。革兰氏阳性细菌释放外毒素，在动物模型和临床环境中均与革兰氏阴性细菌释放内毒素有所区别。另有数据表明，40%-50%脓毒症患者可出现心肌损伤。本课题组前期研究发现革兰氏阳性主要致病菌所致脓毒症患者更易发生循环系统功能障碍或衰竭。基于革兰氏阳性细菌及革兰氏阴性细菌释放外毒素/内毒素在致机体严重感染过程中可能存在的差异，本课题通过分别热灭活金黄色葡萄球菌及热灭活大肠埃希菌腹腔注射构建革兰氏阳性细菌脓毒症及革兰氏阴性细菌脓毒症大鼠模型，评价革兰氏阳性细菌所致脓毒症心肌损伤的表型特征，研究证实革兰氏阳性细菌所致脓毒症更易导致心肌损伤及心肌结构改变，本研究进一步从心肌细胞的损伤、凋亡以及心肌细胞线粒体功能障碍三方面探讨兰氏阳性细菌致脓毒症心肌损伤的可能机制。基于此，在一定程度上可改变脓毒症临床患者的诊疗决策，基于不同感染细菌予以更早期的干预及脏器功能保护策略。