Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Department of Medicine, Indiana University School of Medicine, IN 46202, USA.
Dis Model Mech. 2024 Oct 1;17(10). doi: 10.1242/dmm.050852. Epub 2024 Oct 9.
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 stimulate injury and enhance cardiac pathology in the mdx model, many methods lead to high mortality with 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. mdx and wild-type mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathological 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 compared to wild-type mice. Our findings highlight the utility of challenging mdx mice with low-dose isoproterenol as a valuable model for exploring therapies targeting DMD-associated cardiac pathologies.
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 相关的心肌病不同。尽管有人使用药理学应激来刺激损伤并增强 mdx 模型中的心脏病理学，但许多方法导致高死亡率和可变的心脏结局，并且不能重现人类疾病中所见的结构和功能心脏变化。在这里，我们描述了一种简单有效的方法，使用先进的二维和四维高频超声来监测体内心脏功能障碍的进展，从而增强 mdx 小鼠的心脏表型模型。mdx 和野生型小鼠每天接受低剂量（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 mdx 小鼠的心肌损伤、升高了血清肌钙蛋白 I 水平并增强了纤维化。超声显示 mdx 小鼠的心室功能降低、壁厚度变薄、容积增加和心脏储备减少。我们的研究结果强调了用低剂量异丙肾上腺素挑战 mdx 小鼠作为探索针对 DMD 相关心脏病理学的治疗方法的有价值模型的实用性。
