Cardiac remodeling rather than disturbed myocardial energy metabolism is associated with cardiac dysfunction in diabetic rats
Cardiac remodeling rather than disturbed myocardial energy metabolism is associated with cardiac dysfunction in diabetic rats
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DOI：
10.1016/j.ijcard.2006.01.027
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发表时间：
2007-01-08
影响因子：
3.5
通讯作者：
Fu, Michael
中科院分区：
文献类型：
--
作者：
Bollano, Entela;Omerovic, Elmir;Fu, Michael
背景资料：糖尿病（DM）改变了心脏的能量底物代谢，糖尿病心肌病的早期症状是舒张功能障碍。尽管已知细胞外基质在糖尿病的存在下必须改变，但其局部调节尚未完全阐明。我们的目的是评估在体内左心室（LV）的结构，功能和生物能量学在链脲佐菌素（STZ）诱导的diabetesmellitus.Methods：心脏功能进行了评价，使用超声心动图在麻醉的Sprague-Dawley大鼠12周后注射STZ和年龄匹配的对照组大鼠心房起搏前后。在体内进行P-31磁共振波谱测定磷酸肌酸（PCr）与ATP的比值。用Western blot法检测心肌金属蛋白酶MMP-2、MMP-9、TIMP-1、TIMP-2和胶原蛋白的表达。与对照组相比，糖尿病动物的心脏重量/BW和LV质量/BW比更高（2.3 +/- 08 vs 2.1 +/- 08 mg/g p < 0.05）。糖尿病大鼠的心率较低（293 +/- 20 vs 394 +/- 36 bpm p < 0.05）。糖尿病动物的周向缩短速度和主动脉峰值速度较低，在心房起搏时更为明显。基础PCr/ATP比值两组无差异。糖尿病大鼠的总胶原蛋白更高（3.8 +/- 0.3对2.9 +/- 01 mg/g，p < 0.05）。结论：链脲佐菌素诱导的糖尿病大鼠左室重量比增加，胶原含量增加，MMP-2蛋白表达减少，而PCr/ATP无明显变化。因此，重构而不是紊乱的能量可能是糖尿病心肌病的基础。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Background: Diabetes mellitus (DM) alters the energy substrate metabolism in the heart and the early sign of diabetic cardiomyopathy is the diastolic dysfunction. Although it is known that the extracellular matrix must be altered in the presence of diabetes, its local regulation has not been fully elucidated. Our aim was to evaluate in vivo left ventricular (LV) structure; function and bioenergetics in streptozotocin (STZ) induced diabetes mellitus.Methods: Cardiac function was evaluated using echocardiography in anesthetized Sprague-Dawley rats 12 weeks after injection of STZ and in age-matched control rats before and after atrial pacing. In vivo P-31 magnetic resonance spectroscopy was done to measure the phosphocreatine (PCr) to ATP ratio. Myocardial protein expression of metal loproteinases MMP-2, -9, tissue inhibitor TIMP-1, -2 and collagen was measured using Western blot.Results: Bodyweight (BW) was decreased in diabetic rats. Heart weight/BW and LV mass/BW ratios were higher in diabetic animals compared to controls (2.3 +/- 08 vs 2.1 +/- 08 mg/g p < 0.05). Heart rate was lower in diabetic rats (293 +/- 20 vs 394 +/- 36 bpm p < 0.05). The velocity of circumferential shortening and peak aortic velocity were lower in diabetic animals and were more pronounced during atrial pacing. The basal PCr/ATP ratio was not different in the two groups. Total collagen was higher in diabetic rats (3.8 +/- 0.3 vs 2.9 +/- 01 mg/g, p < 0.05). Protein expression of MMP-2 was significantly diminished in diabetic rats by similar to 60%, while MMP-9, TIMP-1 and -2 were unchanged.Conclusion: Streptozotocin induced diabetes led to increased LV/bodyweight, increased collagen content, and diminished MMP-2 with no change in PCr/ATP. Therefore, remodeling rather than disturbed energetics may underlie diabetic cardiomyopathy. (c) 2006 Elsevier Ireland Ltd. All rights reserved.