Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats
Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats
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DOI：
10.1152/ajpheart.2002.282.1.h138
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发表时间：
2002-01-01
影响因子：
4.8
通讯作者：
Takaki, M
中科院分区：
文献类型：
--
作者：
Abe, T;Ohga, Y;Takaki, M
为了深入了解糖尿病性心肌病的发病机制，我们研究了大鼠左心室机械功和能量学耦合的心功能，大鼠是2型糖尿病（DM）的模型。晚期DM大鼠左室收缩功能、平均冠状动脉血流和冠状动脉血流储备均无差异。机械功和收缩所需的氧气量没有改变，尽管肌凝蛋白同工酶最终从V-1转化为V-3。最大起搏速率从300降至240次/分，左室舒张速率仅在DM晚期显著（P < 0.05）减慢，导致主要由sarco（endo）质网Ca2+- atp酶（SERCA2）消耗的兴奋-收缩偶联中处理总Ca2+的每分钟耗氧量减少，而基础代谢和线粒体氧化磷酸化没有显著变化。重度糖尿病大鼠细胞膜SERCA2蛋白水平显著（P < 0.001）降低。我们得出的结论是，即使在目前的2型糖尿病大鼠中，由于SERCA2表达下降而导致的唯一的肌萎缩性功能障碍也与糖尿病性心肌病的发生有关。
To gain insight into the pathogenesis of diabetic cardiomyopathy, we investigated cardiac function in terms of the coupling of left ventricular mechanical work and the energetics in Otsuka Long-Evans Tokushima Fatty rats, which are well known as a model of type 2 diabetes mellitus (DM). Neither left ventricular systolic function and mean coronary flow nor coronary flow reserve differed even in late DM rats. The amount of oxygen required for mechanical work and contraction was unaltered, although myosin isozyme was finally transformed from V-1 to V-3. The maximum pacing rate was decreased from 300 to 240 beats/ min, and the left ventricular relaxation rate was significantly (P < 0.05) slower only in late DM rats, resulting in decreased oxygen consumption per minute for total Ca2+ handling in excitation-contraction coupling mainly consumed by sarco( endo) plasmic reticulum Ca2+-ATPase (SERCA2) without significant changes in basal metabolism or in mitochondrial oxidative phosphorylation. The protein level of SERCA2 in membranes was significantly (P < 0.001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats.