glp-1通过抑制心肌细胞凋亡和纤维化预防和保护-第三军医大学学报.docVIP

GLP-1改善2型糖尿病大鼠左心室功能障碍 彭莹 李妍 张犁 惠宏襄 510515 广州，南方医科大学国际代谢病中心 【摘要】 目的 观察胰高血糖素样多肽-1（GLP-1）对2型糖尿病大鼠心脏的作用。 方法 高脂高糖膳食合并链脲佐菌素诱导2型糖尿病大鼠模型，体外采用GLP-1直接灌流离体心脏，体内通过给大鼠皮下包埋缓释泵连续灌注GLP-1共 7天，利用langendorff离体心脏灌流系统检测GLP-1对心脏的作用。 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，与正常组相比，LVDP、 RPP、dP/dt max 、m-dP/dt max分别降低40.80%、51.50%、50.87%和52.81%。体外结果显示，与KH灌流液相比GLP-1可快速提高模型大鼠的各项心功能指标，LVDP、P/dt max、m-dP/dt max分别增高54.27%、58.37%和33.31%。体内结果显示，与对照组相比，预防组LVDP、 RPP 、dP/dt max、m-dP/dt max分别增加20.79%、24.04%、37.72%和34.02。治疗组LVDP、RPP、dP/dtmax 、m-dP/dt max分别增加25.36%，10.90%，22.62%和30.07%。 结论 GLP-1能改善2型糖尿病大鼠左心室功能障碍，增加心肌收缩力。 【关键词】 langendorff灌流；2型糖尿病；GLP-1；心脏疾病；大鼠 【中图法分类号】R331.3; R542.2; R587.2; 【文献标识码】A GLP-1 Improve Cardiologic Functions in Type 2 Diabetic Rats PENG Ying, LI Yan, ZHANG Li, HUI Hongxiang. International Center for Metabolic Diseases, Southern Medical University, Guangzhou 510515, China [Abstract] Objective To investigate the efficacy of Glucagon-Like Peptide-1 (GLP-1) on cardiologic functions in type 2 diabetic rats. Methods SD rats were fed with a?high-fat,?high-sugar diet for 4 weeks and intraperitoneally injected with a small dosage of the?streptozotocin (40 mg/kg bw) . Suscceful diabetic rats were subjected to 7 days infusion of human GLP-1(7-36) (30 pmol/kg per min) with Alzet osmotic mini-pump. The hearts of rats?were used?for the?Langendorff heart perfusion?experiments to investigate the GLP-1 efficacy. Results The dysfunction of left ventricular of diabetic rats was recorded at the 10th days after STZ injection. Compared with the normal group, at the 23rd days, the LVDP, RPP, dP/dt Max , m-dP/dt Max in diabetic rats were decreased 40.8%, 51.50%, 50.87%, 52.81% , respectively. In vitro directly perfusing GLP-1 (100nM) improved left ventricular functions. The LVDP, dP/dt Max , m-dP/dt Max were increased 54.27%, 58.37% and 33.31% compared with the control, respectively. There is no significant change on heart rate between groups. In GLP-1 delivered with Alzet osmotic pump group, th