A reliable strategy for establishment of an animal model of diabetic cardiomyopathy: Induction by a high-fat diet combined with single or multiple injections of low-dose streptozotocin

Abstract

BackgroundDiabetic cardiomyopathy (DCM) is one of the leading causes of death in patients with diabetes mellitus (DM). This study aimed to identify a reliable method for establishing an animal model of DCM for investigation of new targets and treatments. MethodsEighty-four 4-week-old male Sprague–Dawley rats were randomly allocated to receive a normal diet or a high-fat diet (HFD) in an approximate ratio of 1:3. At 9 weeks of age, rats in the HFD group received streptozotocin (STZ) 30 mg/kg by intraperitoneal injection and rats in the control group received the same volume of buffer solution. The rodent model of DM was deemed to be successfully established when a random blood glucose measurement was >16.7 mmol/L on three consecutive occasions. If necessary, STZ was readministered. ResultsThree of the 64 rats in the HFD group died after a second STZ injection. DM was induced in 14, 39, and 8 rats after one, two, and three injections, respectively, with cumulative success rates of 21.9 %, 82.8 %, and 95.3 %. Three months later, the rats with DM showed persistent hyperglycemia and insulin resistance and developed histopathological changes indicating cardiac hypertrophy, myocardial fibrosis, and diastolic dysfunction. The metabolic and cardiac histopathological changes were consistent regardless of whether DM was induced by one, two, or three injections of STZ. ConclusionAn HFD combined with one or more intraperitoneal injections of low-dose STZ is a straightforward and reliable method for inducing DCM in rats. When a single dose of STZ fails to induce DM, repeated injections can be considered.