PDF(Pubmed)
Abstract：
Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to enhance the cardiac phenotype in the mdx model, many methods lead to high mortality, variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. For our study, mdx and wild-type (WT) mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathologic assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels, and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes, and diminished cardiac reserve in mdx mice compared to wild-type. Our findings highlight the utility of low-dose isoproterenol in mdx mice as a valuable model for exploring therapies targeting DMD-associated cardiac complications.
摘要：
心肌病是杜氏肌营养不良症（DMD）的主要死亡原因，然而,在DMD的mdx小鼠模型中，心脏表型与DMD相关心肌病不同.尽管有些人使用药理学应激来增强mdx模型中的心脏表型，许多方法导致高死亡率，可变心脏结果，并且不概括人类疾病中看到的心脏结构和功能变化。这里,我们描述了一种简单有效的方法来增强mdx小鼠的心脏表型模型，使用先进的2D和4D高频超声来监测体内心功能不全的进展。对于我们的研究，mdx和野生型(WT)小鼠接受每日低剂量(2mg/kg/天)异丙肾上腺素注射10天。组织病理学评估显示异丙肾上腺素治疗增加了心肌细胞损伤，血清心肌肌钙蛋白I水平升高，mdx小鼠的纤维化增强。超声显示心室功能降低，壁厚减小，数量增加,与野生型相比，mdx小鼠的心脏储备减少。我们的发现强调了低剂量异丙肾上腺素在mdx小鼠中的实用性，作为探索针对DMD相关心脏并发症的疗法的有价值的模型。
结论：这项工作介绍了一种在Duchenne肌营养不良症小鼠模型中模拟心力衰竭的改进方法，并使用先进的成像技术全面描述了潜在的细胞和生理机制。
结论：这项工作介绍了一种在Duchenne肌营养不良症小鼠模型中模拟心力衰竭的改进方法，并使用先进的成像技术全面描述了潜在的细胞和生理机制。
