目的：比较和研究二甲双胍和罗格列酮对实验性糖尿病心肌病（DC）模型大鼠的心脏保护作用。方法：采用高热量饮食加小剂量链脲左菌素（STZ）建立实验性DC 大鼠模型，二甲双胍（140 mg·kg-1）和罗格列酮（2 mg·kg-1）灌胃给药6 周，观察动物一般状态、饮食量、血糖、血脂、心脏结构和功能以及心肌组织脂肪代谢相关指标的变化。结果：（1）二甲双胍和罗格列酮均可显著改善DC 大鼠心肌损伤，降低CK值（P<0.01）；二甲双胍可明显提高DC 大鼠心输出量（P<0.01），罗格列酮可明显改善模型动物左心室最大收缩/舒张变化速率（P<0.05）。（2）二甲双胍和罗格列酮均可显著降低DC 大鼠心室间隔厚度（P<0.01）。（3）二甲双胍可明显改善DC 大鼠一般状态、抑制体质量减轻，减少饮水量（P<0.05）。（4）二甲双胍可显著降低DC 大鼠血糖（FBG、GSP、HbA1c 和FMN）水平（P<0.05 或P<0.01），并可显著降低TG 含量（P<0.01）；罗格列酮可明显降低FBG 和HbA1c 含量（P<0.05），同时可显著降低TG 和LDL 含量，并且明显增加心肌组织FA-β-oxidase 含量（P<0.05）。结论：二甲双胍与罗格列酮在一定程度上可改善DC 大鼠心脏功能紊乱和心肌损伤，二甲双胍在改善DC 大鼠饮食、体质量上显示一定优势。

This study was aimed to compare and investigate protective effects of metformin and rosiglitazone on cardiac dysfunction in experimental diabetic cardiomyopathy (DC) model rats. The experimental DC rat model was induced by feeding high calorie diet plus single intraperitoneal injection of small dosage of streptozotocin (STZ).Then, intragastric administration of metformin (140 mg·kg-1) or rosiglitazone(2 mg·kg-1) was given to DC rats for consecutive 6 weeks. Parameters of general signs, eating amount, blood sugar, blood lipids, heart function, heart structure and lipometabolism of myocardial tissues were measured. The results showed that both metformin and rosiglitazone can obviously improve the myocardial injury of DC model rats and reduce the CK value (P < 0.01).Metformin can obviously increase the cardiac output of DC model rats (P < 0.01). Rosiglitazone can improve the maximum rate of myocardial contraction and diastole of the model rat's left ventricle (P < 0.05). Both metformin and rosiglitazone can decrease interventricular septal thickness (IST) value (P < 0.01). Metformin can obviously improve general signs of DC rats, inhibit body weight loss and reduce water intake (P < 0.05). Metformin can obviously reduce the blood sugar level (FBG, GSP, HbA1c and FMN) of DC rats (P < 0.05, or P < 0.01) as well as the concentration of TG (P < 0.01). Rosiglitazone can reduce the concentration of FBG and HbA1c (P < 0.05).Meanwhile, rosiglitazone can significantly reduce the concentration of TG and LDL as well as obviously increase the myocardial FA-β-oxidase (P < 0.05). It was concluded that both metformin and rosiglitazone can recover the cardiac dysfunction and myocardial injury of DC rats on certain level. Metformin showed more effects on eating amount and body weight improvements of DC rats.

国家自然科学基金委面上项目（30840103）：小檗碱对实验性糖尿病心肌病变的保护作用研究，负责人：洪缨；教育部2013 年度高等学校博士学科点专项科研基金项目（20130013120002）：基于代谢组学和灰色关联分析的糖尿病心肌病发病规律和药物治疗靶点研究，负责人：董世芬。