Steroid treatment causes deterioration of myocardial function in the δ-sarcoglycan-deficient mouse model for dilated cardiomyopathy
Steroid treatment causes deterioration of myocardial function in the δ-sarcoglycan-deficient mouse model for dilated cardiomyopathy
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DOI：
10.1093/cvr/cvn131
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发表时间：
2008-09-01
影响因子：
10.8
通讯作者：
Straub, V.
中科院分区：
文献类型：
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作者：
Bauer, R.;MacGowan, G. A.;Straub, V.
由于口服皮质类固醇对Duchenne型肌营养不良症的肌肉力量有有益的作用，因此有人认为它们也可能是病理相关的肌聚糖病的有效治疗方法。δ-肌聚糖缺陷的小鼠（Sgcd-null）是一个模型，为肢带型肌营养不良症2F（LGMD 2F）和扩张型cardiomyopathy.Methods和结果为了研究口服皮质类固醇对心脏功能的影响，我们治疗8周龄的Sgcd-null小鼠与泼尼松龙（1.5毫克/公斤体重/天口服）8周。使用电导导管通过压力-容积环评估体内心脏功能。我们在Sgcd基因敲除小鼠中发现了基线时代偿良好的心肌病，心肌收缩力降低，前负荷增加，后负荷减少，保持了高心输出量。令人惊讶的是，泼尼松龙治疗的小鼠的心脏血流动力学没有改善，反而恶化，有心室硬化的证据。在组织学上，类固醇治疗后，有增加心肌细胞损伤和增加心肌fibrosis.Conclusion泼尼松龙导致Sgcd基因敲除小鼠心脏血流动力学失代偿，并诱导额外的心脏损伤。基于这些发现，尽管小鼠模型可能无法完全复制LGMD 2F的人类情况，但我们得出结论，在长期使用皮质类固醇的患者中，明确指示了仔细的心脏监测。
Aims As oral corticosteroids have a beneficial effect on muscle strength in Duchenne muscular dystrophy, it has been suggested that they may also be a useful treatment in the pathologically related sarcoglycanopathies. The delta-sarcoglycan-deficient mouse (Sgcd-null) is a model for both limb girdle muscular dystrophy 2F (LGMD2F) and dilated cardiomyopathy.Methods and results To study the effect of oral corticosteroids on cardiac function, we treated 8-week-old Sgcd-null mice with prednisolone (1.5 mg/kg body weight/day orally) for 8 weeks. In vivo cardiac function was assessed by pressure-volume loops using a conductance catheter. We found a well-compensated cardiomyopathy at baseline in Sgcd-null mice with decreased myocardial contractility, increased preload, and decreased afterload, maintaining a high cardiac output. Cardiac haemodynamics, surprisingly, did not improve in prednisolone-treated mice, but instead deteriorated with evidence of ventricular stiffening. On histology, after steroid treatment there was increased myocardial cell damage and increased myocardial fibrosis.Conclusion Prednisolone led to a decompensation of cardiac haemodynamics in Sgcd-null mice and induced additional cardiac damage. On the basis of these findings, although mouse models may not completely replicate the human situation for LGMD2F, we conclude that careful cardiac monitoring is clearly indicated in patients on long-term corticosteroids.