Chopra I J, Huang T S, Hurd R E, Solomon D H
Endocrinology. 1984 Jun;114(6):2039-45. doi: 10.1210/endo-114-6-2039.
We studied the effects of daily ip administration of T4 (200 micrograms/100 g BW) or T3 (50 micrograms/100 g) to the rat (six per group) for 3 days with or without sodium ipodate (6 mg/100 g), propylthiouracil (PTU; 2 mg/100 g), propranolol (0.5 mg/100 g), or amiodarone (2.5 mg/100 g) on cardiac weight, 3',5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine monodeiodinating activity (MA), mitochondrial alpha-glycerophosphate dehydrogenase (alpha GPD), and/or cytosolic ornithine decarboxylase (ODC). T4 treatment caused a 28% increase in cardiac weight, about an 11-fold increase in 3',5'-T2 MA, about a 27% increase in alpha GPD activity, and about a 129% increase in ODC activity. Administration of ipodate with T4 abolished all effects of T4 on the heart. PTU abolished the effect of T4 on alpha GPD and markedly reduced its effect on 3',5'-T2 MA and ODC activity; it had little effect on cardiac hypertrophy caused by T4 treatment. Propranolol reduced the increase in cardiac weight following T4 administration from 28% to 11%, but had a modest or no effect on T4-induced changes in other metabolic variables studied. Amiodarone also reduced the effect of T4 on heart weight, but had little or no influence on 3',5'-T2 MA, the only metabolic variable studied. T3 treatment of the rat caused a 35% increase in heart weight, about a 15-fold increase in 3',5'-T2 MA, about a 35% increase in alpha GPD, and about a 100% increase in ODC activity. Ipodate and PTU reduced the increase in 3',5'-T2 MA following T3 administration, but had no appreciable influence on heart weight, alpha GPD, and/or ODC activity. Propranolol and amiodarone had no significant effect on any of the changes studied after T3 administration. It was concluded that: 1) ipodate markedly lessens or abolishes the effects of T4 on the heart; 2) propranolol and amiodarone decrease cardiac hypertrophy in response to T4 administration, but have little or no effect on metabolic changes due to T4; 3) PTU curtails the metabolic effects of T4 on the heart but has little effect on cardiac hypertrophy; 4) none of the drugs studied affects cardiac changes occurring after T3 administration. The changes observed in 3',5'-T2 MA after ipodate and PTU treatment may have been a result of direct interaction of the drugs with the deiodinase.
我们研究了每日腹腔注射甲状腺素（T4，200微克/100克体重）或三碘甲状腺原氨酸（T3，50微克/100克）给大鼠（每组6只），连续3天，同时给予或不给予碘番酸钠（6毫克/100克）、丙硫氧嘧啶（PTU；2毫克/100克）、普萘洛尔（0.5毫克/100克）或胺碘酮（2.5毫克/100克）对心脏重量、3',5'-二碘甲状腺原氨酸（3',5'-T2）向3'-单碘甲状腺原氨酸的单脱碘活性（MA）、线粒体α-甘油磷酸脱氢酶（αGPD）和/或胞质鸟氨酸脱羧酶（ODC）的影响。T4处理使心脏重量增加28%，3',5'-T2的MA增加约11倍，αGPD活性增加约27%，ODC活性增加约129%。碘番酸钠与T4一起给药消除了T4对心脏的所有影响。PTU消除了T4对αGPD的影响，并显著降低了其对3',5'-T2的MA和ODC活性的影响；它对T4处理引起的心脏肥大影响很小。普萘洛尔将T4给药后心脏重量的增加从28%降低到11%，但对T4诱导的其他所研究代谢变量的变化影响不大或没有影响。胺碘酮也降低了T4对心脏重量的影响，但对所研究的唯一代谢变量3',5'-T2的MA影响很小或没有影响。用T3处理大鼠使心脏重量增加35%，3',5'-T2的MA增加约15倍，αGPD增加约35%，ODC活性增加约100%。碘番酸钠和PTU降低了T3给药后3',5'-T2的MA的增加，但对心脏重量、αGPD和/或ODC活性没有明显影响。普萘洛尔和胺碘酮对T3给药后所研究的任何变化均无显著影响。得出的结论是：1）碘番酸钠显著减轻或消除T4对心脏的影响；2）普萘洛尔和胺碘酮可减轻T4给药引起的心脏肥大，但对T4引起的代谢变化影响很小或没有影响；3）PTU可减少T4对心脏的代谢影响，但对心脏肥大影响很小；4）所研究的药物均不影响T3给药后发生的心脏变化。碘番酸钠和PTU处理后3',5'-T2的MA中观察到的变化可能是药物与脱碘酶直接相互作用的结果。
