目的 觀察胰高血糖素樣多肽-1（GLP-1）對大鼠2型糖尿病性心肌病心肌損傷的影響。方法 采用高脂高糖膳食合并鏈脲佐菌素（40 mg/kg）誘導的方法建立2型糖尿病大鼠模型。將糖尿病大鼠模型隨機分為模型組和GLP-1組，采取皮下包埋緩釋泵，分別給兩組大鼠連續(xù)灌注生理鹽水或GLP-1 30 pmol/(kg?min?1)，7 d后，處死取心臟，利用Langendorff離體心臟灌流系統(tǒng)進行心臟功能檢測和心肌細胞形態(tài)學觀察。結(jié)果 糖尿病大鼠在建模成功后第10天出現(xiàn)左心室功能異常。3周后，與正常相比，左室發(fā)展壓（LVDP）、心率–左心室發(fā)展壓乘積值（RPP）、dp/dtmax、m-dp/dtmax分別降低40.80%、51.50%、50.87%、52.81%；心肌組織炎性細胞浸潤增加，血管周圍及心肌細胞間纖維化增加，心肌細胞凋亡指數(shù)增加。GLP-1處理組LVDP、RPP、dp/dtmax、m-dp/dtmax分別較模型組增加25.36%、10.90%、22.62%、30.07%，心肌細胞炎癥、凋亡減少，心肌組織間及血管周圍纖維化降低，差異具有統(tǒng)計學意義（P＜0.05）。結(jié)論 糖尿病可直接誘發(fā)以間質(zhì)性纖維化、代償性纖維化、炎癥細胞浸潤和凋亡細胞增多為特點的心肌組織損傷，形成糖尿病性心肌病。體內(nèi)持續(xù)釋放GLP-1可緩解糖尿病引發(fā)的心肌組織損傷，對其心肌組織有保護作用。

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.

國家重大科學研究計劃（973計劃）項目（2011CB504006）；高等學校博士學科點專項科研基金資助項目（20104433110014）；松山湖重點扶持科研項目（2010B025）