丙硫氧嘧啶对高甲状腺素血症大鼠心肌的保护作用及其机制

Protective effect and mechanism of propylthiouracil on myocardial injury associated with hyperthyroxinemia in rats

目的 探讨丙硫氧嘧啶对高甲状腺素血症大鼠心肌的保护作用及其机制。方法 将60只成年健康SD大鼠，随机分为高甲状腺素模型组（甲亢组，n＝20）、高甲状腺素模型＋丙硫氧嘧啶组（治疗组，n＝20）和正常对照组（n＝20），高甲状腺素大鼠模型采用左旋甲状腺素钠灌胃法[0.5 mg/（kg·d），连续2周]建立。观察干预后第0、2、4、6、8周各组大鼠心率、体重变化，检测血中三碘甲状腺氨酸（T3）、甲状腺素（T4）水平，检测血和心肌组织中血管紧张素转化酶（ACE）、血管紧张素Ⅱ（AngⅡ）水平，计算心脏重量/体重比值，光镜下观察心肌组织病理学改变。结果 （1）与正常对照组比较，甲亢组0、2、4、6、8周各时间点心率显著增高、体重显著降低，血T3[8周：（1.79±0.24）比（1.26±0.22） g/L；t＝3.256，P＝0.017]、T4[8周：（116.7±11.1）比（56.1±8.7） g/L；t＝8.594，P＝0.000]水平显著升高，血和心肌组织中ACE[血8周：（22.7±4.5）比（14.4±3.5） g/L，t＝2.912，P＝0.027；组织8周：（46.1±3.9）比（30.5±3.6） g/L；t＝5.878，P＝0.001]、AngⅡ[血8周：（486±16）比（442±14） g/L；t＝4.139，P＝0.006；组织8周：（846±15）比（793±13） g/L；t＝5.340，P＝0.002]水平显著升高，心脏重量/体重比值显著变大，光镜下心肌组织病理学改变明显。（2）与甲亢组比较，治疗组2、4、6、8周各时间点心率显著降低、体重显著升高，血T3[8周：（1.38±0.21）比（1.79±0.24） g/L；t＝2.571，P＝0.042]、T4[8周：（69.6±11.8）比（116.7±11.1） g/L；t＝5.815，P＝0.001]水平显著降低，血和心肌组织中ACE[血8周：（15.0±4.3）比（22.7±4.5） g/L；t＝2.912，P＝0.027；组织8周：（35.1±3.7）比（46.1±3.9） g/L；t＝4.092，P＝0.006]、AngⅡ[血8周：（450±15）比（486±16） g/L；t＝3.283，P＝0.017；组织8周：（796±14）比（846±15） g/L；t＝4.874，P＝0.003]水平显著降低，8周心脏重量/体重比值显著减小，光镜下心肌组织病理学改变减轻。结论 ACE-AngⅡ-肾素-血管紧张素（RAS）系统在高甲状腺素血症致心肌损害中发挥作用，丙硫氧嘧啶可能通过调节ACE-AngⅡ-RAS系统发挥心肌保护作用。

Objective To investigate the protective effect and mechanism of propylthiouracil on myocardial injury associated with hyperthyroxinemia in rats.Methods Sixty SD rats were randomly divided into the hyperthyroxinemia group （n=20）, hyperthyroxinemia＋ propylthiouracil group （n=20） and the normal control group （n=20）. The rat model of high thyroid hormone was established by the method of sodium [0.5 mg/（kg·d）, 4 weeks]. The changes of heart rate and body mass were observed at 0, 2, 4, 6 and 8 weeks after the intervention. The levels of blood 3, 5, 3′-triiodothyronine （T3） and thyroxin （T4） were detected. The levels of angiotensin-converting enzyme （ACE） and angiotensin Ⅱ （AngⅡ） in blood and myocardium were measured and the ratio of heart/body weight was calculated. The pathological changes of myocardium were observed under light microscope.Results （1） As compared with the normal control group, the heart rate at 0, 2, 4, 6 and 8 weeks of the hyperthyroidism group was significantly increased, the body weight was significantly decreased, the blood T3 [at 8th week： （1.79±0.24） vs. （1.26±0.22） g/L; t=3.256, P=0.017] and T4 [8 weeks： （116.7±11.1） vs. （56.1±8.7） g/L; t=8.594, P=0.000] levels were significantly increased, ACE [blood of 8 weeks： （22.7±4.5） vs. （14.4±3.5） g/L; t=2.912, P=0.027. Myocardium of 8 weeks： （46.1±3.9） vs. （30.5±3.6） g/L; t=5.878, P=0.001] and AngⅡ [blood of 8 weeks： （486±16） vs. （442±14） g/L; t=4.139, P=0.006. Myocardium of 8 weeks： （846±15） vs. （793±13） g/L; t=5.340, P=0.002] levels in blood and myocardium were significantly increased; the ratio of heart/body mass was significantly increased; and the pathological changes of myocardium were obvious under light microscope. （2） As compared with hyperthyroidism group, the heart rate in the hyperthyroxinemia＋ propylthiouracil group was decreased significantly at 2, 4, 6 and 8 weeks, the body weight increased significantly, the levels of blood T3 [8 weeks： （1.38±0.21） vs. （1.79±0.24） g/L; t=2.571, P=0.042] and T4 [8 weeks： （69.6±11.8） vs. （116.7±11.1） g/L; t=5.815, P=0.001] were significantly decreased, the levels of ACE [blood of 8 weeks： （15.0±4.3） vs. （22.7±4.5） g/L; t=2.912, P=0.027. Myocardium of 8 weeks： （35.1±3.7） vs. （46.1±3.9） g/L; t=4.092, P=0.006] and AngⅡ [blood of 8 weeks： （450±15） vs. （486±16） g/L; t=3.283, P=0.017. Myocardium of 8 weeks： （796±14） vs. （846±15） g/L; t=4.874, P=0.003] in blood and myocardium were significantly decreased, the ratio of heart/body weight at 8 weeks was significantly reduced, the pathological changes of myocardium were alleviated.Conclusion The ACE-AngⅡ-renin-aangiotensin system （RAS） system plays a role in myocardial damage caused by hyperthyroxemia. Propylthiouracil may regulate ACE-Ang II-RAS system and play a protective effect on myocardial hyperthyroxinemia in rats.