RAS阻断剂对实验性高甲状腺素毒性兔心房电生理和离子通道表达的影响.docVIP

RAS阻断剂对实验性高甲状腺素毒性兔心房电生理和离子通道的影响 肖培林，高崇翰，范晋奇，龙 毅，殷跃辉（） [摘要]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（n=10）正常对照甲状腺素、贝那普利厄贝沙坦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通过心内电生理仪测定心房有效不应期，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（α1C??和 α1D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76.63±4.44)ms]和厄贝沙坦79.00±4.95)ms]心房有效不应期甲状腺素75.13±5.41)ms]无明显。L型Ca2+通道贝那普利1.15±0.24)和厄贝沙坦1.08±0.17) 明显高于甲状腺素0.56±0.11)，P0.05，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。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。 [关键词] 甲状腺功能亢进；肾素-血管紧张素系统；心房颤动；心房重构； Effect of RAS Blockade on Atrial Electrophysiology and Ion Channel of Experimental Hyperthyroid Rabbit Xiao Peilin， Gao Chonghan， Fan Jinqi， Long Yi， Yin Yue-hui（ From the Second Affiliated Hospital of Chongqing University of Medical Sciences， Chongqing ， 400010） [ABSTRACT ] Objective：The purpose of this study was to evaluate the effect of renin angiotensin systemRAS) blockade on hyperthyroid induced chronic atrial electrical and ion channel remodeling in experimental thyrotoxic rabbits. Methods：Forty rabbits were assigned to four groupssham group, thyroxine group, benazepril group and irbesartan group. Intraperitoneal injection levorotatory thyroxine (Levothyroxine, L-Thy) establish rabbit thyroxine toxicity model. Benazepril or irbesartan were administered orally combined with L-Thy in benazepril group and irbesartan group. 4 weeks later，performed burst stimulation to induce atrial fibrillation(AF). The atrial effective refractory period (AERP) and the AF vulnerability were evaluted. The real-time PCR was used for measuring the mRNA expression of L-Ca channel related subunits(α1C and α1D) and Ito related channel subunits（kv1.4kv4.2 and kv4.3）.?The protein expression of Cav1.3 and Kv4.2 was detected by Western blotting. Results: No