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目的探讨游离脂肪酸(FFA)在2型糖尿病(DM)中对心肌能量底物代谢以及心功能的影响。方法采用高脂喂养(40%脂肪)加小剂量链脲佐菌素(STZ)建立2型DM大鼠模型,成模后随机分为2组实验对照组继续高脂喂养,实验治疗组给予高脂喂养加罗格列酮(RSG)3mg·kg-1·d-1治疗2周。正常对照组为普通饮食(12%脂肪)喂养。3组大鼠均左室插管检测心功能后进行30min等容体外心脏灌注,测定葡萄糖摄取量及3H2O计数,评估心肌葡萄糖和脂肪酸氧化率。结果模型鼠的血糖、血浆胰岛素及FFA水平均高于正常鼠,与临床2型DM的代谢特征相似。实验对照组与正常对照组比较,心肌葡萄糖总摄入量明显减少[(30.7±4.0)∶(69.0±5.7)μmol/g干重,P<0.01],葡萄糖氧化率降低(12%∶25%,P<0.05)、软脂肪酸氧化率增加(88%∶75%,P<0.05);同时,左室舒张末期压(EDP)明显增加,-dp/dtmax降低,+dp/dtmax无明显改变。与实验对照组比较,实验治疗组大鼠血糖明显改善、血浆胰岛素和FFA显著降低;心肌葡萄糖的总摄入量升高,葡萄糖和软脂肪酸的氧化率分别为21%和79%;同时EDP和-dp/dtmax均改善(P<0.05)。结论2型DM循环FFA水平增高可以导致心肌能量底物代谢的异常和左室舒张功能的降低。早期使用RSG可改善胰岛素抵抗、降低FFA,能提高心肌对葡萄糖的利用、抑制脂肪酸氧化,有助于保护2型DM的心功能。
Objective To investigate the effects of free fatty acid (FFA) on myocardial energy metabolism and cardiac function in type 2 diabetes mellitus (DM). Methods Type 2 diabetic rats were induced by high-fat diet (40% fat) and low-dose streptozotocin (STZ). The rats were randomly divided into experimental and control groups, and then fed with high-fat diet. Fat-fed plus rosiglitazone (RSG) 3 mg · kg-1 · d-1 for 2 weeks. Normal control group fed a normal diet (12% fat). The left ventricular intubation was used to measure the cardiac function in all three groups, and the isokinetic cardiopulmonary perfusion was performed within 30 minutes. The glucose uptake and the 3H2O count were measured to evaluate the myocardial glucose and fatty acid oxidation rate. Results The blood glucose, plasma insulin and FFA levels of model mice were higher than those of normal mice, which were similar to those of clinical type 2 DM. Compared with the control group, the total myocardial glucose intake was significantly decreased in the experimental control group [(30.7 ± 4.0) vs (69.0 ± 5.7) μmol / g dry weight, P <0.01] , P <0.05). The rate of oxidation of soft fatty acid increased (88%: 75%, P <0.05). Meanwhile, EDP increased significantly, dp / dtmax decreased and dp / dtmax increased. Compared with the experimental group, the blood glucose of the experimental group was significantly improved, the plasma insulin and FFA were significantly decreased; the total myocardial glucose intake was increased, the oxidation rates of glucose and soft fatty acid were 21% and 79% respectively; meanwhile EDP and -dp / dtmax improved (P <0.05). Conclusion The increase of circulating FFA in type 2 DM can lead to the abnormal metabolism of myocardial energy and the decrease of left ventricular diastolic function. Early use of RSG improves insulin resistance, decreases FFA, improves myocardial glucose utilization, inhibits fatty acid oxidation, and helps to protect heart function in Type 2 DM.