心肌梗死后细胞外间质容积与左室重构机制的实验研究

The purpose of this study design is to investigate the mechanism of extracellular matrix volume (ECV) of left ventricle as well as the myocardial fiber arrangement (MFA) in the process of negative ventricular remodeling post acute and chronic myocardial infarction. On the basis of our preliminary research, by using the Chinese mini-swine for making acute and chronic myocardial infarction models, we designed a randomized double-blind controlled study to quantitively analysis the ECV in the area of infarction, peri-infarction and remote infarction. And we will also evaluate the MFA by diffusion tensor imaging as well as the relationship between the ECV and MFA in the mechanism in negative ventricular remodeling post myocardial infarction.The results of this study is expected to achieve noninvasive quantitative ECV imaging in vivo, reveal relations between ECV and myocardial systolic and diastolic function under different physiological and pathological conditions, make clear the evolution process of ECV with the time after myocardial infarction, reveal the relationship between myocardial microstructure changes and the myocardial remodeling and obtain preliminary understanding the effects of ECV and scar tissue in the morphology and function in the area of peri-infarction. The expected achievements of the research will be very important for clinical treatment programs of myocardial infarction, especially for the prevention and treatment of negative left ventricular remodeling, thereby improving the patient's prognosis. It will also provide the scientific basis for the related basic and clinical research, in particular, in the targeted drug therapy of inhibiting the synthesis of extracellular matrix (mainly of type I collagen).

针对急、慢性心肌梗死后左室心肌及其心肌外间质组织在左室负性重构中的机制问题，本申请课题在前期研究基础上，以中华小型猪的急、慢性心肌梗死模型为研究对象，采用双盲随机对照的研究设计方式，研究急、慢性心肌梗死后左室梗死区、梗死周边区及远离梗死区细胞外间质容积（ECV）的变化，并与相应区域的心肌纤维走行变化相结合，确定两者在左室重构中的意义及相互关系。项目预期将实现活体ECV的无创定量影像学成像，揭示不同生理病理条件下ECV与心肌收缩与舒张功能之间的关系，明确心肌梗死后ECV的演化进程，揭示心肌微观结构变化与心肌重塑之间的关系，初步了解ECV与瘢痕组织对周围正常心肌在形态与功能上的影响。项目的研究成果对于心肌梗死后临床治疗方案，特别是针对负性左室重构的预防及治疗，改善患者的预后具有重要意义。可以为相关基础与临床研究，特别是抑制细胞外间质合成增加的靶向药物治疗提供科学依据。

针对急、慢性心肌梗死后左室心肌及其心肌外间质组织在左室负性重构中的机制问题，本申请课题在前期研究基础上，以中华小型猪的急、慢性心肌梗死模型为研究对象，采用双盲随机对照的研究设计方式，研究急、慢性心肌梗死后左室梗死区、梗死周边区及远离梗死区细胞外间质容积（ECV）的变化，动物实验发现非对比剂增强 T1 mapping测量的心肌梗死范围与传统LGE与病理TTC染色之间的相关系数分别为0.9091和0.906, 具有非常高的一致性。继而临床研究发现T1 mapping、T2 mapping及T1&T2 mapping诊断急性心肌梗死的敏感性分别为90.0%、88.3%和91.7%, 特异性分别为87.4%, 77.6% 和91.3%， ROC曲线下面积分别为0.925±0.020, 0.889±0.025 和0.951±0.14。在非缺血心脏病方面，课题组发现T1 mapping/ECV及DWI/ADC可评估肥厚型心肌病的心肌纤维化，T1 mapping/ECV技术可早期发现高血压心肌纤维化。研究成果对于缺血及非缺血心脏病诊断及确定临床治疗方案，特别是针对负性左室重构的预防及治疗，改善患者的预后具有重要意义。可以为相关基础与临床研究，特别是抑制细胞外间质合成增加的靶向药物治疗提供科学依据。