犬房颤模型心房纤维化对心房重塑和炎症水平的影响

Effect of atrial fibrosis on atrial structural remodeling and inflammation in atrial fibrillation canines

目的研究心房纤维化在犬心房颤动(房颤)中对心房重塑及炎症水平的影响。方法 30只犬随机分为3组:房颤组(6只)、纤维化组(12只)及药物组(12只)。房颤组进行心房快速起搏(provided atrial tachypacing,ATP)8周。纤维化组在进行ATP的同时诱导心房结构重塑。药物组犬除进行ATP和诱导心房结构重塑外,口服羟尼酮药物治疗。分别于起搏前及起搏后4周及8周进行C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平检测、超声心动图、电生理检查及心房组织学检查。结果相对于房颤组,纤维化组胶原容积分数、左心房直径、房颤维持时间、房颤诱发率均明显升高;药物组较房颤组无明显差异。起搏4周时纤维化组CRP水平较房颤组明显升高[(434.99±135.26)ng/mL vs(346.67±81.09)ng/mL,P<0.05]。起搏8周时纤维化组CRP、IL-6及TNF-α水平明显高于房颤组及药物组(P<0.05),药物组与房颤组间各炎症因子水平无明显差异(P>0.05)。炎症因子水平与左心房直径及胶原容积分数呈正相关关系。结论犬房颤过程中心房纤维化加重心房重塑及炎症反应,羟尼酮减轻心房结构重塑,并降低炎症水平,提示羟尼酮可能在房颤治疗中起重要作用。

Objective To evaluate the effects of atrial fibrosis on atrial remodeling and inflammation in an atrial fibrillation （AF） canine model. Methods We studied 30 canines, randomly divided into 3 groups： group A （n=6）, group B （n=12） and group C （n=12）. A pacemaker was implanted in group A, and provided atrial tachypacing （ATP） for 8 weeks. Group B received ATP and atrial structural remodeling. Besides ATP and left atrial injection, oral hydronidone was administered for the pacing period in group C. We performed C-reactive protein （CRP）, tumor necrosis factor-α （TNF-α）, and interleukin-6 （IL-6） expression detection, echocardiography, AF vulnerability study and atrial fibrosis measurement at baseline, and 4 and 8 weeks after ATP. Results Compared to group A, group B showed significant elevation in collagen volume fraction, left atrial diameters, AF duration and percent of burst attempts leading to AF episodes. There was no significant difference between group C and group A. The elevation of CRP in group B was greater than that in group A in 4 weeks after ATP （434.99±135.26 vs 346.67±81.09 ng/mL, P〈0.05）. Eight weeks after ATP, group B had more significant increases in CRP, IL-6 and TNF-α than other groups. There was no significant difference between group A and group C in any inflammatory factor. The inflammatory factor levels had positive associations with left atrial diameter and collagen volume fraction. Conclusion Atrial fibrosis contributes to atrial remodeling and elevation in inflammation, whereas hydronidone attenuates such effects, implicating that hydronidone may play an important role in the management of AF.