基于核素心肌脂肪酸代谢显像研究心肌缺血再灌注损伤非缺血心肌能量代谢障碍及其机制

Myocardial ischemia-reperfusion injury (MIRI) is an important factor for poor efficacy of reperfusion therapy and adverse prognosis in patients with acute coronary syndrome. Myocardial energy metabolism disorder is a possible mechanism of MIRI, and fatty acid is the main source of myocardial energy. The previous study from our research group have found that systolic dysfunction and energy metabolism disorder occur in non-infarcted myocardium after myocardial infarction. Pre-experimental confirmed that fatty acid metabolism was reduced in ischemic-associated myocardium in miniature pig MIRI model. Previous studies have suggested that a series of pathological changes such as inflammation, edema and changes in mitochondria-related protein levels were present in non-ischemic myocardium during MIRI. Therefore, we hypothesized that energy metabolism disorder also occurs in non-ischemic myocardium during MIRI, which may be a potential mechanism of MIRI. Our research group will use nuclear myocardial fatty acid metabolism imaging to quantitatively, dynamically study the changes of energy metabolism in non-ischemic myocardium at different time points before and after modeling based on a miniature pig MIRI model. In addition, the structure and quantity of mitochondria, expression of myocardial fatty acid metabolism related protein and its mRNA, and the changes of ATP were observed and detected in vitro. These studies will explore the molecular mechanism of energy metabolism disorder in non-ischemic myocardium, which could provide new targets and new perspectives for the prevention and treatment of MIRI.

心肌缺血再灌注损伤（MIRI）是影响冠心病急性冠脉综合征患者再灌注治疗效果及预后的重要因素，心肌能量代谢障碍是其可能机制，脂肪酸是心肌能量的主要来源。课题组前期研究发现心肌梗死后血流灌注正常（非梗死区）心肌存在收缩功能异常和能量代谢障碍，预实验证实小型猪MIRI模型缺血相关心肌存在脂肪酸代谢减低。相关研究提示MIRI非缺血心肌存在炎症、水肿及线粒体相关蛋白水平改变等一系列病理改变。据此我们推测MIRI非缺血心肌也存在能量代谢障碍，这可能是MIRI的潜在机制。课题组拟构建小型猪MIRI模型，运用核素心肌脂肪酸代谢显像动态、定量研究建模前、后不同时间点非缺血心肌能量代谢的变化，并离体观察线粒体结构及数量，检测心肌脂肪酸代谢相关蛋白及其mRNA的情况以及ATP的变化，探索非缺血心肌能量代谢障碍对应的分子机制，以期为MIRI防治提供新靶点及新思路。

心肌缺血再灌注损伤（MIRI）是影响冠心病急性冠脉综合征患者再灌注治疗效果及预后的重要因素，心肌能量代谢障碍是其可能机制，脂肪酸是心肌能量的主要来源。课题组前期研究发现心肌梗死后血流灌注正常（非梗死区）心肌存在收缩功能异常和能量代谢障碍，预实验证实小型猪MIRI模型缺血相关心肌存在脂肪酸代谢减低。相关研究提示MIRI非缺血心肌存在炎症、水肿及线粒体相关蛋白水平改变等一系列病理改变。据此我们推测MIRI非缺血心肌也存在能量代谢障碍，这可能是MIRI的潜在机制。课题组构建小型猪MIRI模型，运用核素心肌脂肪酸代谢显像动态、定量研究建模前、后不同时间点非缺血心肌能量代谢的变化，发现18F-FTHA PET心肌代谢显像可无创、定量评价心肌脂肪酸代谢水平，动态监测心肌能量代谢障碍。左心室心肌18F-FTHA摄取率在MIRI后2小时即出现显著降低，1天达到最低点，5天时有所恢复，在随后的30天随访期间无显著变化。MIRI后心肌能量代谢重构不仅仅局限于缺血心肌，非缺血心肌也存在不同程度的能量代谢重构，左心室作为一个整体参与MIRI后心肌能量代谢重构。MIRI后左室舒张功能异常是其早期表现。MIRI早期缺血心肌及非缺血心肌脂肪酸代谢减低与MIRI后舒张功能障碍具有显著相关性，明确了MIRI后左心室非缺血心肌能量代谢重构与心肌功能的关系，阐明MIRI后心肌能量代谢重构是左室舒张功能障碍的机制之一。本项目创新性地从心肌能量底物代谢的角度揭示MIRI的发病机制，为MIRI的防治提供了新的潜在治疗靶点。