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目的:本研究旨在探讨甲状腺激素(三碘甲状腺原氨酸,T3)替代治疗能否改善心功能和甲状腺功能,并探索最佳治疗剂量,为临床提供初步试验数据。方法:腹腔注射异丙肾上腺素(ISO)诱导心肌梗死后心力衰竭(心衰)伴甲状腺功能紊乱的动物模型,并检测血清中肌钙蛋白I(cTnI),以确定动物发生心肌梗死。将心衰大鼠随机分为4组:无治疗对照组(C-group)、低剂量T3治疗组(10μg/kg,L-group)、中剂量T3治疗组(30μg/kg,M-group)和高剂量T3治疗组(60μg/kg,H-group),连续给予T3治疗3d。定期行心脏超声心动图检查,检测游离T3(FT3)和游离T4(FT4)浓度,32d实验结束处死动物,取心脏做氯化三苯基四氮唑染色(TTC染色)。结果:①ISO诱导应激性心肌梗死模型大鼠心衰并伴有FT3、FT4降低,cTnI升高和超声心动图的改变。②给予T3替代治疗后,与C-group相比,L-group心功能明显改善,心脏超声短轴缩短率(FS)上升显著(P<0.01),血清中FT3和FT4下降幅度明显低于其他组(P<0.05);与L-group相比,M-group和H-group血清中FT3和FT4下降值、FS降低更明显,以H-group为甚;③大鼠心肌组织TTC染色提示心肌梗死重量指数各组间无明显差异,表明T3补充治疗对心功能的改善作用不依赖于显著降低心肌梗死面积。结论:严重心衰动物会出现甲状腺功能紊乱,予以适当小剂量T3补充治疗后能改善心脏功能,剂量过大反而使心功能受损。
Objective: This study aimed to investigate whether thyroid hormone (triiodothyronine, T3) replacement therapy can improve cardiac function and thyroid function, and explore the best therapeutic dose for the clinical preliminary data. Methods: The animal model of heart failure (CHF) with thyroid dysfunction was induced by intraperitoneal injection of isoprenaline (ISO) and the serum cTnI was detected to determine the occurrence of myocardial infarction. The rats with heart failure were randomly divided into 4 groups: C-group, low dose T3 group (10μg / kg, L-group) and middle dose T3 group (30μg / kg, M group) And high-dose T3 treatment group (60μg / kg, H-group), continuous treatment of T3 for 3d. Cardiac echocardiography was performed on a regular basis. The free T3 (FT3) and free T4 (FT4) concentrations were measured. Animals were sacrificed on the end of 32 days. TTC staining was performed on the heart. Results: ① ISO induced heart failure in rats with stress myocardial infarction accompanied by decreased FT3, FT4, elevated cTnI and echocardiographic changes. Compared with C-group, heart function of L-group was significantly improved, shortening rate of cardiac ultrasound (FS) increased significantly (P <0.01), and the decrease of FT3 and FT4 in serum was significantly lower than that of C-group (P <0.05). Compared with L-group, the decrease of FT3 and FT4 in serum of M-group and H-group showed that the decrease of FS was more obvious, especially H-group. Infarct weight index was not significantly different among the groups, indicating that the effect of T3 supplementation on cardiac function does not depend significantly on the reduction of myocardial infarct size. Conclusion: Thyroid dysfunction may occur in severely weakened animals. After a small dose of T3 is added, cardiac function may be improved. Excessive doses may cause impaired cardiac function.