心外膜脂肪垫在低强度颈动脉窦电刺激干预心房颤动中的作用及机制研究

Pericardial fat pad is closely associated with atrial fibrillation (AF). Pericardial fat pad comprises atrial autonomic ganglionated plexus and large amount of adipocytes, The correlation of ganglionated plexus with AF is widely acknowledged and correlation of adiopocytes with AF is revealed recently. However, whethere there is interactions between ganglionated plexus and adiopocytes remains unknown. .Carotid baroreflex stimulation (CBS) has been applied to treat resistant hypertension and heart failure by inhibiting symathetic nervous activity. Our previous study showed that low-level CBS (LL-CBS) could reverse atrial electrical remodeling induced by acute rapid atrial pacing and induction of AF by inhibiting activity of left stellate ganglion in canine models, and prevent rats from high-fat diet induced visceral fat accumulation and metabolic abnormalities..We hypothesize that there may be a cross-talk between ganglionated plexus and adipose tissue. Modulation of the adipose tissue of the epicardial fat pad may underlies the mechnisms of LL-CBS suppressing AF. .To test this hypothesis, we plan to establish chronic AF canine models by rapid right atrial pacing and apply LL-CBS which is 80% of the lowest effective voltage to reduce blood pressure. Then, we will observe the effects of LL-CBS on incidence of AF, the effects of atrial electrical, structural and autonomic remodeling, and investigate the role of adipokines and cytokines secreted by epicardial adipose tissue as well as the interactions of adipose tissue with ganglionated plexus in LL-CBS inhibiting AF. The possible signaling pathway will also be investigated. The results will provide new insights into the role of epicardial adipose tissue and autonomic neural remodeling in the underlying mechanisms of AF and provide new strategies to prevent AF.

心外膜脂肪垫与心房颤动(房颤)关系密切。心外膜脂肪垫中存在心房自主神经节和大量脂肪细胞，前者与房颤的关系为人熟知，后者与房颤的关系也渐被揭示，但神经节和脂肪有无相互作用尚不清楚。.颈动脉窦电刺激(CBS)可干预交感神经张力而被用于顽固型高血压和心衰的治疗。我们近期发现低强度CBS可通过抑制左星状神经节活性发挥抗犬房颤的作用；对高脂喂养的肥胖大鼠的机体代谢异常有改善作用。.我们假设:心外膜脂肪垫中自主神经和脂肪相互作用，共同促进房颤的发生发展；对心外膜脂肪垫中脂肪组织的干预也是低强度CBS抑制房颤的机制之一。.本项目拟用快速心房起搏制作犬慢性房颤模型，观察低强度CBS对房颤的影响，对心房电重构、结构重构及神经重构的作用，从脂肪因子、炎症因子及脂肪-自主神经相互作用的角度探究心外膜脂肪垫在低强度CBS干预房颤中的作用及机制。有望从心外膜脂肪和自主神经的角度为探索房颤的机制和干预策略提供新思路。

心外膜脂肪垫中存在心房自主神经节和大量脂肪细胞，二者均与心房颤动（房颤）的关系密切，但神经节和脂肪有无相互作用尚不清楚。颈动脉窦电刺激(CBS)可干预交感神经张力而被用于顽固型高血压和心衰的治疗。我们前期发现低强度CBS可通过抑制左星状神经节活性发挥抗犬房颤的作用；对高脂喂养的肥胖大鼠的机体代谢异常有改善作用。.本项目旨在从脂肪因子及脂肪-自主神经相互作用的角度探究心外膜脂肪垫在低强度CBS干预房颤中的作用及机制。.本项目采用长期快速右心房起搏（600bpm）制作犬慢性房颤模型，观察低强度CBS对房颤的影响，对心房电重构、结构重构及神经重构的作用。结果显示持续快速右心房起搏8周可成功构建犬慢性房颤模型，主要表现为自发房性心律失常事件显著增加，左房明显扩大，左房射血分数明显降低，以及左房出现明显的结构重构、电重构和神经重构。低强度CBS可显著降低自发房性心律失常负荷，改善心房的结构和功能异常，降低心肌纤维化水平，改善心房电生理特性，降低房颤诱发率，抑制左侧星状神经节和心房自主神经节重构。同时本项目发现，低强度CBS可抑制房颤犬心外膜脂肪垫中脂肪因子瘦素的过度分泌。本项目进一步将瘦素注射入正常犬心外膜脂肪垫，观察瘦素作用于心房自主神经节对心房电重构和神经重构的影响。结果显示，瘦素可增加房颤诱发率，提高左侧星状神经节活性。.上述研究结果说明，心外膜脂肪垫中脂肪因子瘦素与自主神经之间存在相互作用，共同促进房颤的发生，低强度CBS可通过抑制自主神经重构和脂肪因子分泌来发挥抗房颤的作用。