论文部分内容阅读
目的研究肾素-血管紧张素系统(renin angiotensin system,RAS)在甲状腺素诱导的心房电重构和离子通道重构中的作用,探讨RAS阻断剂对甲状腺素诱导的心房重构的影响。方法 40只新西兰大白兔分为4组(n=10):正常对照、甲状腺素、贝那普利及厄贝沙坦干预组。腹腔注射左旋甲状腺素(Levothyroxine,L-Thy)建立兔甲状腺素毒性模型,贝那普利组和厄贝沙坦组同时给予贝那普利或厄贝沙坦。4周后,通过心内电生理仪测定心房有效不应期,连续高频刺激诱发心房颤动(atrial fibrillation,AF),评价心房频率适应性和AF诱发率,荧光定量PCR检测L型Ca2+通道(Cav1.2和Cav1.3亚基)和Ito电流相关亚基(kv1.4、kv4.2和kv4.3)mRNA表达,Western blot检测L型Ca2+通道α亚基和kv4.2蛋白表达。结果贝那普利和厄贝沙坦明显降低AF诱发率并明显改善高甲状腺素诱导的频率适应性变化。贝那普利组(76.63±4.44)ms和厄贝沙坦组(79.00±4.95)ms心房有效不应期较甲状腺素组(75.13±5.41)ms无明显延长(P>0.05)。L型Ca2+通道蛋白表达在贝那普利组(1.15±0.24)和厄贝沙坦组(1.08±0.17)明显高于甲状腺素组(0.56±0.11)(P<0.01),但对高甲状腺素引起的Ito电流相关亚基变化无明显抑制作(P>0.05)。结论 RAS可能参与了高甲状腺素性诱导的心房电生理和离子通道改变,贝那普利和厄贝沙坦可以改善L-Thy诱导的心房电重构和离子通道重构,并降低高甲状腺素致AF性。
Objective To investigate the role of renin angiotensin system (RAS) in thyroxine-induced atrial electrical remodeling and ion channel remodeling and to explore the effect of RAS blockade on thyroxine-induced atrial remodeling. Methods 40 New Zealand white rabbits were divided into 4 groups (n = 10): normal control, thyroxine, benazepril and irbesartan intervention group. The model of thyroxine toxicity was established by intraperitoneal injection of Levothyroxine (L-Thy), and benazepril or irbesartan were given to both benazepril and irbesartan groups. Four weeks later, the atrial fibrillation (AF) was evaluated by intracardiac electrophysiology, and the atrial fibrillation (AF) was evaluated by continuous high frequency stimulation. The atrial fibrillation rate and AF induction rate were evaluated. The expression of L-type Ca2 + Cav1.2 and Cav1.3 subunits) and Ito current related subunits (kv1.4, kv4.2 and kv4.3) mRNA expression were detected by Western blot L-type Ca2 + channel alpha subunit and kv4.2 protein expression. Results Benazepril and irbesartan significantly reduced the rate of AF induction and significantly improved the high frequency of thyroid hormone-induced changes in fitness. The atrial effective refractory period in benazepril group (76.63 ± 4.44) ms and irbesartan group (79.00 ± 4.95) ms was no longer than that in thyroxine group (75.13 ± 5.41) ms (P> 0.05). The expression of L-type Ca2 + channel protein in the benazepril group (1.15 ± 0.24) and irbesartan group (1.08 ± 0.17) was significantly higher than that in the thyroxine group (0.56 ± 0.11) (P <0.01) Induced Ito current-related subunit changes were not significantly inhibited (P> 0.05). Conclusions RAS may be involved in the changes of atrial electrophysiology and ion channel induced by high thyroxine. Benaopril and irbesartan can improve L-Thy-induced atrial electrical remodeling and ion channel remodeling, and reduce high-thyroxine-induced AF Sex.