Weltman Nathan Y, Ojamaa Kaie, Schlenker Evelyn H, Chen Yue-Feng, Zucchi Riccardo, Saba Alessandro, Colligiani Daria, Rajagopalan Viswanathan, Pol Christine J, Gerdes A Martin
Department of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, United States of America.
Center for Heart and Lung Research, North Shore-LIJ Health System, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
Mol Med. 2014 May 1;20(1):302-12. doi: 10.2119/molmed.2013.00040.
Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 μg/mL T3; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T3 treatment (3 months post-DM induction), left ventricular (LV) function was assessed by echocardiography and LV pressure measurements. Despite normal serum thyroid hormone (TH) levels, STZ/N treatment resulted in reductions in myocardial tissue content of THs (T3 and T4: 39% and 17% reduction versus C, respectively). Tissue hypothyroidism in the DM hearts was associated with increased DIO3 deiodinase (which converts THs to inactive metabolites) altered TH transporter expression, reexpression of the fetal gene phenotype, reduced arteriolar resistance vessel density, and diminished cardiac function. Low-dose T3 replacement largely restored cardiac tissue TH levels (T3 and T4: 43% and 10% increase versus STZ/N, respectively), improved cardiac function, reversed fetal gene expression and preserved the arteriolar resistance vessel network without causing overt symptoms of hyperthyroidism. We conclude that cardiac dysfunction in chronic DM may be associated with tissue hypothyroidism despite normal serum TH levels. Low-dose T3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.
甲状腺功能障碍在糖尿病患者中很常见，可能导致相关的心脏功能障碍。然而，关于甲状腺功能低下状态对糖尿病患者心脏的影响程度和病理生理后果，人们所知甚少。通过注射烟酰胺（N；200mg/kg），随后注射链脲佐菌素（STZ；65mg/kg），在成年雌性Sprague Dawley（SD）大鼠中诱导糖尿病。在STZ/N注射后1个月，将大鼠随机分为以下几组（每组N = 10）：STZ/N组或STZ/N + 0.03μg/mL T3组；年龄匹配的经载体处理的大鼠作为非糖尿病对照（C）组。在T3治疗2个月后（糖尿病诱导后3个月），通过超声心动图和左心室压力测量评估左心室（LV）功能。尽管血清甲状腺激素（TH）水平正常，但STZ/N治疗导致心肌组织中THs（T3和T4）含量降低（与C组相比，分别降低39%和17%）。糖尿病心脏中的组织甲状腺功能减退与DIO3脱碘酶增加（将THs转化为无活性代谢物）、TH转运体表达改变、胎儿基因表型重新表达、小动脉阻力血管密度降低以及心脏功能受损有关。低剂量T3替代在很大程度上恢复了心脏组织TH水平（T3和T4：与STZ/N组相比，分别增加43%和10%），改善了心脏功能，逆转了胎儿基因表达，并保留了小动脉阻力血管网络，且未引起明显的甲状腺功能亢进症状。我们得出结论，尽管血清TH水平正常，但慢性糖尿病中的心脏功能障碍可能与组织甲状腺功能减退有关。低剂量T3替代似乎是一种安全有效的辅助治疗方法，可减轻和/或逆转实验性糖尿病引起的心脏重塑和功能障碍。
