Long-term amiodarone treatment causes cardioselective hypothyroid-like alteration in gene expression profile
Long-term amiodarone treatment causes cardioselective hypothyroid-like alteration in gene expression profile
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DOI：
10.1016/j.ejphar.2007.09.039
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发表时间：
2008-01-14
影响因子：
5
通讯作者：
Kodama, Itsuo
中科院分区：
文献类型：
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作者：
Shi, Rong-qian;Lee, Jong-Kook;Kodama, Itsuo
胺碘酮的长期心脏效应类似于甲状腺功能减退症的许多方面。因此，胺碘酮的抗心律失常潜力可能是药物诱导的局部甲状腺功能减退的结果。为了研究这一有争议的问题，我们比较了胺碘酮治疗的大鼠和甲状腺功能减退大鼠心脏中的基因表达谱。Wistar雄性大鼠随机分为3组(n=6~8)：对照组、全身性甲状腺功能减退症(甲减)组和胺碘酮治疗组(胺碘酮150 mg/kg/d，灌胃，4周)。进行心电图记录、基因芯片和Northern印迹分析。与甲状腺功能减退症一样，胺碘酮也可引起心电图RR间期和QT间期显著延长。对8435个基因进行的左室心肌基因芯片分析表明，甲状腺功能减退症和胺碘酮在表达谱上有显著的相似性(R=0.63，p
The long-term cardiac effects of amiodarone resemble many aspects of hypothyroidism. The anti-arrhythmic potential of amiodarone may therefore be the result of a drug-induced, local hypothyroid-like condition. To investigate this controversial issue, we compared gene expression profiles in the hearts of rats treated with amiodarone with those of rats with hypothyroidism. Wistar male rats were assigned to 3 groups (n = 6-8): Control, systemic hypothyroidism (Hypothyroidism) and amiodarone treatment (Amiodarone, 150 mg/kg/day, p.o., 4 weeks). Electrocardiogram (ECG) recordings, gene profiling by DNA microarray and Northern blotting were carried out. Amiodarone, like Hypothyroidism, caused significant prolongation of RR and QT intervals in ECGs. Microarray analysis of 8435 genes in the left ventricular myocardium revealed a significant similarity in expression profiles between Hypothyroidism and Amiodarone (R=0.63, p