适配子MR分子成像对急性心肌梗死后TNF-α/TNFR心室双向重构作用分析

Post-acute myocardial infarction (AMI) inflammatory response may be the origin of left ventricular (LV) remodeling. The inflammatory pathway TNF-α/TNFR has a positive/negative bidirectional effect on inflammatory cytokines in post-AMI. However, current research barely explained the relationship of the pathway activation level at each stage of post-AMI with the cytokines, myocardium and LV remodeling. This project intends to use our established AMI model to dynamically observe the TNF-α aptamer molecular imaging in vivo: (1) The myocardial TNF-α/TNFR pathway spatial distribution and dynamic process at each stage of post-AMI in infarction area, border area and remote area; (2) The dynamic dose-effect between post-AMI TNF-α/TNFR expression and inflammatory cytokines, inflammatory cells, myocardial cells, and intercellular substance. Clarify the role of TNF-α/TNFR pathway in the evolution of LV remodeling. This study will provide an in vivo continuous, dynamic and targeted imaging method for the detection and assessment of post-AMI inflammation evolution and LV remodeling. Providing the theoretical basis for the prediction, early signs and intervention of post-AMI heart failure.

急性心肌梗死（AMI）后炎症反应可能为心室重构的始发因素。现存研究已证实TNF-α/TNFR炎症通路对AMI后心肌组织下游炎症因子存在正/负双向作用。但目前静态的研究方法难以阐释该通路激活水平对AMI后各时期下游炎症通路、心肌组织及心室重构的发生发展及因果关系。本项目拟应用我们已建立的AMI模式动物，通过TNF-α核酸适体分子影像在体内动态观察和研究：（1）AMI后心肌内TNF-α/TNFR通路在梗死区、周围区及远端空间分布规律及急性至慢性阶段的动态变化过程；（2）AMI后心肌内TNF-α/TNFR表达对炎症因子和细胞、心肌细胞、间质以及心室双向性重构的量效关系，明确该通路在趋使心室重构演进中的作用和地位。本研究将为检测和评估AMI后炎症与心室重构演进提供一个活体内连续、动态、特异的影像学方法，为预测AMI后心衰提供风向标和早期干预的理论基础。

研究发现急性心肌缺血损伤（AMI）后炎症反应可能为心室重构的始发因素。本项目在我们已建立的AMI模式动物基础上，通过TNF-α适配子分子影像在体内动态观察和研究，明确了AMI后心肌内TNF-α/TNFR通路分布为梗死区高于周围区高于远端空间分布规律，自急性至慢性阶段呈亚急性期上升，慢性期下降改变。AMI后心肌内TNF-α/TNFR表达为慢性期心室负性重构的独立预测因子。本研究将为检测评估AMI后活体内TNF-α/TNFR介导的炎性损伤提供一个连续、动态的影像学评估方法，为早期干预治疗提供新的理论基础。