心房结构重构在房颤的维持和复发中起着关键性的作用，其基本特征是心房间质纤维化。高同型半胱氨酸血症是心、脑血管疾病强大的独立危险因素，近来研究显示它与房颤的发生也密切相关。然而，高同型半胱氨酸参与房颤结构重构的可能机制，目前并不清楚。本课题在前期研究基础上提出假设，高同型半胱氨酸可能通过激活MMPs，诱导心房肌细胞外基质的重构，影响缝隙连接蛋白的重塑，促进心房间质纤维化的形成，从而参与房颤的发生。本课题拟建立高同型半胱氨酸犬模型，比较不同浓度下的心房不应期、房颤诱发率、房颤维持率，MMPs、TIMPs、缝隙连接蛋白和胶原蛋白的mRNA和蛋白表达，胶原蛋白和缝隙连接蛋白的容积分数检测，以及MMPs的免疫荧光定位检测。本假设的验证将有助于阐明高同型半胱氨酸参与房颤发生的分子机制，揭示新的干预靶点，为房颤临床防治提供新的理论依据和思路。

Atrial structural remodeling plays a key role in the maintenance and recurrence of atrial fibrillation(AF), with interstitial fibrosis as its basic characteristics. Hyperhomocysteinemia is a strong independent risk factor for cardio- and cerebrovascular diseases. Recent studies demonstrate it also has a close link with the development of AF. However, the detailed mechanism behind this relationship is still unclear. Herein, based on our previous study results, the hypothesis is proposed that hyperhomocysteinemia may induce the extracellular matrix and connexin remodeling via activating MMPs, contributing to the interstitial fibrosis and the development of AF. A dog model of hyperhomocysteinemia is to be created, aiming at comparing the atrial refractory period, the ability to induce and maintain AF under different concentrations of high homocysteine, examining the mRNA and protein expressions of MMPs, TIMPs, connexins and collagens, the volume fraction of collagens and connexins, and investigating the immunofluorescence distribution of MMPs. The validation of the hypothesis will help to illustrate the molecular mechanism of high homocysteine in the development of AF, identify novel targets for intervention, and provide new theoretical basis for AF management.