目的 观察胰高血糖素样多肽-1（GLP-1）对大鼠2型糖尿病性心肌病心肌损伤的影响。方法 采用高脂高糖膳食合并链脲佐菌素（40 mg/kg）诱导的方法建立2型糖尿病大鼠模型。将糖尿病大鼠模型随机分为模型组和GLP-1组，采取皮下包埋缓释泵，分别给两组大鼠连续灌注生理盐水或GLP-1 30 pmol/(kg?min?1)，7 d后，处死取心脏，利用Langendorff离体心脏灌流系统进行心脏功能检测和心肌细胞形态学观察。结果 糖尿病大鼠在建模成功后第10天出现左心室功能异常。3周后，与正常相比，左室发展压（LVDP）、心率–左心室发展压乘积值（RPP）、dp/dtmax、m-dp/dtmax分别降低40.80%、51.50%、50.87%、52.81%；心肌组织炎性细胞浸润增加，血管周围及心肌细胞间纤维化增加，心肌细胞凋亡指数增加。GLP-1处理组LVDP、RPP、dp/dtmax、m-dp/dtmax分别较模型组增加25.36%、10.90%、22.62%、30.07%，心肌细胞炎症、凋亡减少，心肌组织间及血管周围纤维化降低，差异具有统计学意义（P＜0.05）。结论 糖尿病可直接诱发以间质性纤维化、代偿性纤维化、炎症细胞浸润和凋亡细胞增多为特点的心肌组织损伤，形成糖尿病性心肌病。体内持续释放GLP-1可缓解糖尿病引发的心肌组织损伤，对其心肌组织有保护作用。

Objective To investigate the beneficial effect of glucagon-like peptide 1 (GLP-1) on myocardial injury in type 2 diabetic rats. Methods SD rats were fed with high-fat and high-sugar diet for 4 weeks and intraperitoneally injected with a small dosage of streptozotocin (STZ, 40 mg/kg). Established diabetic rats were divided into diabetic model group and GLP-1 treatment group. Two groups were subjected to 7 d infusion of saline or GLP-1 (30 pmol/kg per min) with mini-pump. After sacrificed, isolated rats hearts were perfused to the Langendorff technique for evaluating the cardiac function and observing morphology. Results The dysfunction of left ventricular of diabetic rats was recorded at day 10 after STZ injection. Compared with the normal group, at day 23, the LVDP, RPP, dp/dtmax, and m-dp/dtmax in diabetic rats were decreased 40.80%, 51.50%, 50.87%, and 52.81%, respectively. Morphologically, there was a significant increase of inflammatory and apoptosis cells. Masson’s trichrome staining showed that both perivascular and interstitial collagen contents were increased. In GLP-1 group, the LVDP, RPP, dp/dtmax, and m-dp/dtmax were increased 25.36%, 10.90%, 22.62%, and 30.07%, respectively. Morphologically, there was a significant reduction of inflammatory cells and apoptotic index. Masson’s trichrome staining showed that GLP-1 suppressed both perivascular and interstitial collagen contents in LV with statistically significant difference (P＜0.05）. Conclusions These results demonstrated that type 2 diabetic myocardial injury showed compensatory fibrosis, interstitial fibrosis, increased inflammatory cells and apoptosis. Continous infusion GLP-1 improved the left ventricular dysfunctions and myocardial contractility.

国家重大科学研究计划（973计划）项目（2011CB504006）；高等学校博士学科点专项科研基金资助项目（20104433110014）；松山湖重点扶持科研项目（2010B025）