Wallenberg Laboratory, Sahlgrenska Academy at Gothenburg University Hospital 413 45 Gothenburg, Sweden.
Int J Cardiol. 2007 Jan 8;114(2):195-201. doi: 10.1016/j.ijcard.2006.01.027.
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.
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 ³¹P magnetic resonance spectroscopy was done to measure the phosphocreatine (PCr) to ATP ratio. Myocardial protein expression of metalloproteinases MMP-2, -9, tissue inhibitor TIMP-1, -2 and collagen was measured using Western blot.
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 ≈ 60%, while MMP-9, TIMP-1 and -2 were unchanged.
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.
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迹象是舒张功能障碍。虽然已知在糖尿病存在的情况下细胞外基质必须发生改变，但它的局部调节尚未完全阐明。我们的目的是评估链脲佐菌素（STZ）诱导的糖尿病大鼠体内左心室（LV）的结构、功能和生物能量学。
在 STZ 注射后 12 周，对麻醉的 Sprague-Dawley 大鼠进行超声心动图评估心功能，并在年龄匹配的对照大鼠在心房起搏前后进行评估。通过体内 ³¹P 磁共振波谱测量磷酸肌酸（PCr）与 ATP 的比值。使用 Western blot 测量心肌金属蛋白酶 MMP-2、-9、组织抑制剂 TIMP-1、-2 和胶原蛋白的蛋白表达。
糖尿病大鼠体重（BW）下降。与对照组相比，糖尿病动物的心脏重量/BW 和 LV 质量/BW 比值更高（2.3±0.8 与 2.1±0.8 mg/g，p<0.05）。糖尿病大鼠的心率较低（293±20 与 394±36 bpm，p<0.05）。糖尿病动物的圆周缩短速度和主动脉峰值速度较低，在心房起搏时更为明显。两组的基础 PCr/ATP 比值无差异。糖尿病大鼠的总胶原含量较高（3.8±0.3 与 2.9±01 mg/g，p<0.05）。糖尿病大鼠的 MMP-2 蛋白表达显著减少约 60%，而 MMP-9、TIMP-1 和 -2 不变。
链脲佐菌素诱导的糖尿病导致 LV/体重增加、胶原含量增加、MMP-2 减少，而 PCr/ATP 没有变化。因此，糖尿病心肌病的发生可能是重构而不是能量代谢紊乱。
