基于心脏磁共振细胞外容积成像研究Galectin-3在心房颤动诱导心肌间质纤维化中的作用及其机制

Atrial fibrillation (AF) is one of the most important predisposing factors of heart failure (HF), and the left ventricular myocardial interstitial fibrosis is the key physiological basis. It is found that inflammatory mediator Galectin-3 may play an important role in it, however, the specific mechanisms and related molecular pathways remain to be clarified, and there is no early and quantitative noninvasive evaluation method in clinic. In the early stage, we used cardiac magnetic resonance (ECV) imaging to confirm the increased left ventricular ECV in patients with AF, and it is closely related to the increase of Galectin-3 level, AF may promote the occurrence of myocardial interstitial fibrosis by up regulating plasma Galectin-3 level. Based on the above, this study intends to establish canine AF model, evaluate the accuracy of ECV imaging in the assessment of left ventricular fibrosis in AF; on this basis, by regulating the expression level of Galectin-3, observe the changes in the expression of downstream signaling JAK/STAT molecules and the difference of the degree of myocardial fibrosis, "delineate" the Galectin-3 signal path in this process. This study is based on the imaging method, explore the mechanism of HF induced by AF, it is expected to provide a potential target for prevention and treatment of AF associated HF.

心房颤动（房颤）是心力衰竭（心衰）重要的诱发因素之一，而左室心肌间质纤维化是其关键的病生理基础。研究发现炎症介质Galectin-3可能在其中发挥重要作用，但具体机制及相关分子通路尚待明确，且临床上缺乏早期、定量化的无创评价方法。本项目前期应用心脏磁共振细胞外容积（ECV）成像，证实房颤患者左室ECV明显增加，且与血浆Galectin-3水平升高密切相关。据此，本研究拟构建犬房颤模型，通过组织病理学检测心肌胶原纤维含量，验证ECV成像对房颤左室纤维化定量评估的准确性；在此基础上，通过调控Galectin-3表达水平，观察下游信号通路JAK/STAT分子表达的变化及相应心肌纤维化程度的差异，“勾画”此过程中Galectin-3信号路径。本研究基于影像学手段，探索房颤诱导心肌纤维化致心衰的作用机制，有望为预防和治疗房颤相关心衰提供潜在干预靶点。

心房颤动（房颤）与心力衰竭（心衰）关系密切且互为因果，左心室心肌间质纤维化是二者共同的病生理基础。本研究构建犬房颤模型，通过对模型犬心脏进行系列磁共振检查，并结合组织病理学检测左心室心肌胶原纤维含量，验证心脏磁共振细胞外容积（ECV）成像对房颤左心室纤维化定量评估具有良好的准确性，心脏磁共振成像，特别是ECV序列可以作为临床上早期、定量化评估房颤患者左心室心肌纤维化的无创评价方法。在此基础上，本研究进而通过调控Galectin-3表达水平，观察到下游信号通路JAK/STAT分子表达量与左心室心肌纤维化程度明显相关，验证了JAK/STAT 信号通路参与Galectin-3的表达并影响左心室心肌纤维化的程度。本研究为炎症介质Galectin-3在房颤左心室心肌纤维化过程中的具体机制，特别是其中的分子通路的阐明提供了新的证据。本研究通过系列磁共振检查，观察房颤模型犬逐渐发生心功能不全后心肌纤维化程度的变化，结合动态观察Galectin-3表达水平的变化，为房颤诱导心肌纤维化导致心衰的作用机制提供了基于影像学手段的依据，根据我们的研究结果显示，调控Galectin-3表达水平可能是预防和治疗房颤相关心衰的干预靶点。

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