甲亢源性心房颤动与肾素-血管紧张素系统相关发病机制的研究

目的:研究高甲状腺素导致房颤与肾素-血管紧张素系统(RAS)相关的发病机制。方法:左旋甲状腺素经兔腹腔注射,制作甲亢源性房颤易患模型,同时厄贝沙坦经胃管灌胃,乳兔左心房肌细胞培养药物干预;检测房颤诱发率、左心房肌细胞凋亡情况,检测RAS相关的细胞因子,凋亡蛋白表达情况。结果:中途撤药组、厄贝沙坦组、对照组房颤诱发率低于持续给药组(P<0.05)。中途撤药组、持续给药组、厄贝沙坦组心肌细胞凋亡率、ACE m RNA相对表达量、ACE血浆浓度、表达量、AngⅡ血浆浓度、表达量均高于对照组,持续给药组高于中途撤药组、厄贝沙坦组(P<0.05)。中途撤药组、持续给药组、厄贝沙坦组PARP、caspase3相对表达量均高于对照组,持续给药组高于中途撤药组、厄贝沙坦组(P<0.05)。AngⅡ组药物干预后左心房肌细胞凋亡率高于对照组、甲状腺素组(P<0.05)。结论:高甲状腺素所致的房颤发病机制可能是间接过度激活RAS,循环、组织AngⅡ表达增高,后者诱导心房肌细胞凋亡,左心房发生电-解剖重构。

Study on the Pathogenesis of Hyperthyroid Atrial Fibrillation and Renin-Angiotension System

Objective: To study the pathogenesis of high thyroxine induced atrial fibrillation and renin-angiotension system(RAS).Methods: The model of hyperthyroid atrial fibrillation was made by injecting levothyroxine into abdominal cavity of rabbits, at the same time, irbesartan was infused into the stomach through gastric tube, and drug intervention was carried out in the left atrial myocyte culture of suckling rabbits. The induction rate of atrial fibrillation and apoptosis of left atrial myocytes were measured, RAS related cytokines and apoptotic protein expression were measured. Results: The induced rate of atrial fibrillation in the withdrawal group, irbesartan group and control group was lower than that in the continuous administration group(P<0.05). The cardiomyocyte apoptosis rate, relative expression of ACE m RNA, ACE plasma concentration, expression amount, AngⅡ plasma concentration and expression amount in the with drawal group, the continuous administration group and the irbesartan group were higher than those in the control group, and those in the continuous administration group were higher than those in the withdrawal group and the irbesartan group(P<0.05). The relative expression of PARP and caspase3 in the withdrawal group, the continuous administration group and the irbesartan group were higher than those in the control group, and those in the continuous administration group were higher than those in the withdrawal group and the irbesartan group(P<0.05). The apoptosis rate of left atrial myocytes in AngⅡ group was higher than that in control group and thyroxine group after drug intervention(P<0.05). Conclusion: One of the pathogenesis of high thyroxine induced atrial fibrillation may be that it indirectly overactivates RAS, increases the expression of AngⅡin circulation and tissue, the latter induces apoptosis of atrial myocytes and electrical anatomical remodeling of left atrium.