Xu Yanjiani, Zhang Jialiang, Zhou Jing, Zhang Yaoyu, Huang Fangyang, Chen Mao
Department of Cardiology, West China Hospital, Sichuan University; Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University; Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University.
Department of Cardiology, West China Hospital, Sichuan University; Laboratory of Cardiac Structure and Function, Institute of Cardiovascular Diseases, West China Hospital, Sichuan University; Cardiac Structure and Function Research Key Laboratory of Sichuan Province, West China Hospital, Sichuan University;
J Vis Exp. 2024 Nov 29(213). doi: 10.3791/67189.
The underlying pathophysiological mechanisms of diabetic cardiomyopathy (DbCM), a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM), remain poorly understood. The myocardial toxicity associated with T2DM is attributed to factors such as lipotoxicity, glucotoxicity, oxidative stress, reduced cardiac efficiency, and lipoapoptosis. Compared to rats, mice offer greater accessibility, cost-effectiveness, and broader applicability for animal experiments. Insulin resistance and impaired insulin secretion are crucial factors in the pathophysiology of T2DM. We introduce a novel nongenetic murine model that replicates the progression of human DbCM induced by a combination of high-fat diet (HFD) feeding and streptozotocin (STZ) injection. In this study, we used wild-type C57BL/6J mice, administering an HFD regimen for 12 weeks, followed by intraperitoneal injections of STZ for an additional 12 weeks to induce characteristic manifestations of T2DM. We conducted oral glucose tolerance tests and measured serum insulin concentrations to confirm the development of insulin resistance and insufficient insulin secretion. Cardiac structure and function were rigorously assessed through noninvasive transthoracic echocardiography. Pathological characteristics were evaluated through Masson's trichrome staining and wheat germ agglutinin (WGA) staining, revealing pathological features related to DbCM. Therefore, we provide a robust and versatile method for establishing a nongenetic murine model of DbCM.
糖尿病性心肌病（DbCM）是2型糖尿病（T2DM）患者死亡的主要原因，其潜在的病理生理机制仍知之甚少。与T2DM相关的心肌毒性归因于脂毒性、糖毒性、氧化应激、心脏效率降低和脂肪凋亡等因素。与大鼠相比，小鼠在动物实验中具有更高的可及性、成本效益和更广泛的适用性。胰岛素抵抗和胰岛素分泌受损是T2DM病理生理学的关键因素。我们引入了一种新型非基因小鼠模型，该模型可复制由高脂饮食（HFD）喂养和链脲佐菌素（STZ）注射联合诱导的人类DbCM的进展。在本研究中，我们使用野生型C57BL/6J小鼠，给予12周的HFD方案，随后腹腔注射STZ 12周，以诱导T2DM的特征性表现。我们进行了口服葡萄糖耐量试验并测量血清胰岛素浓度，以确认胰岛素抵抗和胰岛素分泌不足的发展。通过无创经胸超声心动图对心脏结构和功能进行了严格评估。通过Masson三色染色和麦胚凝集素（WGA）染色评估病理特征，揭示了与DbCM相关的病理特征。因此，我们提供了一种建立DbCM非基因小鼠模型的强大且通用的方法。
