肾脏去神经化对房颤合并肾脏损害的凝血和心房内皮功能影响和机制研究

Chronic renal impairment (RI) has a close correlation with atrial fibrillation (AF). Stroke was the most common and severe complication of AF. RI could raise the risk of thrombosis and bleeding. The coagulation mechanism of AF combined with RI is still unclear. We have established in vivo model of RI with renal insufficiency combined with AF in a large animal successfully, the outcomes suggested that RI facilitates the initiation of AF. Renal denervation (RDN) significantly reduced AF inducibility and shortened its duration. RND attenuated sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) activity, atrial inflammation and fibrosis, which were associated with endothelial function and thrombogenesis. We hypothesized that RDN may decrease the endothelial dysfunction induced by RI and AF. The main purpose of this study is to observe the effects and possible mechanism of RI on blood coagulation and endothelial function of AF through animal experiment, which will provide references for anticoagulation therapy of the patients with AF and RI. Renal denervation (RDN) therapy which is a kind of method to reduce the activity of SNS, may become a breakthrough point for the treatment of AF combined with RI.

肾脏损害和房颤发生密切相关，二者相互促进形成恶性循环。卒中是房颤最常见和严重的并发症。肾脏损害既可以导致血栓形成，也可以导致出血。房颤合并肾脏损害患者的凝血相关机制尚不明确。本课题组已通过栓塞肾脏血管成功建立了肾脏损害的模型，并通过心房快速刺激建立阵发性房颤动物模型，初步证实了肾脏损害易于房颤的发生，发现肾脏去神经化可以减少合并肾脏损害房颤的发生，抑制交感神经、RAAS系统激活，抑制心房炎症、纤维化。交感神经、RASS激活，心房炎症、纤维化可导致内皮损伤，那么肾脏去神经化有可能通过抑制以上因素减轻内皮损伤和血栓形成。本课题拟通过建立肾脏损害合并房颤模型，探索肾脏损害合并房颤对实验动物凝血和心房内皮功能影响和相关机制，为临床上肾脏损害合并房颤患者血栓和出血风险管控提供参考和依据，并探索肾脏去神经化是否可减轻房颤合并肾脏损害导致的内皮损伤，为临床上合并肾脏损害房颤的防治提供新的思路。

背景与目的：.肾功能不全(RI)纳入房颤(AF)出血风险评分，未纳入血栓风险评分。目前尚不清楚房颤患者RI是否会增加血栓形成的风险。此外，还没有研究探讨这种联系。因此，本研究的目的是通过动物模型观察肾脏损害合并房颤对犬左心房内皮功能的影响。.方法.实验动物随机分为RI组、RI联合AF组、AF组和对照组。采用单侧明胶海绵栓塞左肾动脉3个月建立慢性肾损伤的体内模型。连续刺激右心房3小时，建立房颤模型。比较各组动物的内皮功能、凝血纤溶指数、炎症指数、肾素-血管紧张素-醛固酮系统(renin - angiotensinaldosterone system, RAAS)活性。.结果单侧肾动脉栓塞3个月可引起慢性肾缺血损伤和中度RI。快速刺激右心房3小时，建立犬房颤模型。与RI组、AF组及对照组相比，RI+AF组动物内皮功能受到严重影响。RI+AF组凝血因子升高，凝血及纤溶指标紊乱，炎症及RAAS激活。.结论.1.成功建立慢性肾脏损害合并中度肾功能不全活体大动物模型，并在此基础上成功建立房颤模型。慢性肾损害合并中度肾功能不全伴房颤内皮功能损伤严重，血栓形成风险明显增加。