Department of Cardiology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), NO. 1 Jiazi Road, Lunjiao, Shunde District, Foshan City, Guangdong 528308, China; Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde) NO. 1 Jiazi Road, Lunjiao, Shunde District, Foshan City, Guangdong 528308, China.
State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Life Sci. 2024 Dec 1;358:123161. doi: 10.1016/j.lfs.2024.123161. Epub 2024 Oct 19.
Diabetic 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.
Eighty-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.
Three 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.
An 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.
糖尿病心肌病（DCM）是糖尿病（DM）患者死亡的主要原因之一。本研究旨在寻找一种可靠的方法来建立 DCM 动物模型，以研究新的靶点和治疗方法。
84 只 4 周龄雄性 Sprague-Dawley 大鼠随机分为正常饮食组或高脂肪饮食（HFD）组，比例约为 1:3。9 周龄时，HFD 组大鼠给予链脲佐菌素（STZ）30mg/kg 腹腔注射，对照组大鼠给予相同体积的缓冲液。当连续 3 次随机血糖测量值>16.7mmol/L 时，认为大鼠 DM 模型建立成功。如果需要，可重复给予 STZ。
HFD 组 64 只大鼠中有 3 只在第二次 STZ 注射后死亡。1 次、2 次和 3 次注射后分别有 14、39 和 8 只大鼠成功诱导 DM，累积成功率分别为 21.9%、82.8%和 95.3%。3 个月后，DM 大鼠持续出现高血糖和胰岛素抵抗，并出现心肌肥厚、心肌纤维化和舒张功能障碍等组织病理学改变。无论 STZ 诱导 DM 是 1 次、2 次还是 3 次注射，其代谢和心脏组织病理学变化均一致。
HFD 联合 1 次或多次小剂量腹腔注射 STZ 是诱导大鼠 DCM 的一种简单可靠的方法。如果单次 STZ 注射不能诱导 DM，可以考虑重复注射。
