Zhao Shu-Mei, Wang Yong-Liang, Guo Chun-Yan, Chen Jin-Ling, Wu Yong-Quan
Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, XiCheng District, Beijing, China.
Cardiovasc Diabetol. 2014 Apr 9;13:75. doi: 10.1186/1475-2840-13-75.
Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca2+ homeostasis. This study investigated the effects of alterations in Ca2+ homeostasis and sarcoplasmic reticulum Ca2+-associated proteins on cardiac function in the development of diabetic cardiomyopathy.
Sprague-Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca2+ spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca2+-associated proteins were assessed by Western blotting.
Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca2+ spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca2+ spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-2ATPase (SERCA) and Na+/Ca2+ exchanger (NCX1) were decreased, together with quantitative alterations in Ca2+regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats.
Ca2+ sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca2+-associated proteins.
糖尿病性心肌病中的心脏功能障碍可能与异常的钙稳态有关。本研究调查了钙稳态改变和肌浆网钙相关蛋白对糖尿病性心肌病发展过程中心脏功能的影响。
将Sprague-Dawley大鼠分为4组（每组n = 12）：对照组，以及链脲佐菌素诱导的糖尿病大鼠模型组，分别在4周、8周或12周后进行检查。分别通过超声心动图和血流动力学检查对心脏结构和功能进行评估。分离心肌细胞，通过引入荧光染料Fluo-4形成自发钙火花图像，并用共聚焦扫描显微镜获取。通过蛋白质免疫印迹法评估钙相关蛋白的表达。
超声心动图和血流动力学测量显示，心脏功能障碍与糖尿病的进展相关，这也与钙火花频率逐渐但显著下降相关（在4周、8周和12周糖尿病组中）。然而，相对于对照组，钙火花衰减时间常数显著增加。糖尿病大鼠中，兰尼碱受体2（RyR2）、肌浆网钙-2-ATP酶（SERCA）和钠/钙交换体（NCX1）的表达降低，同时钙调节蛋白FKBP12.6和受磷蛋白的定量改变也逐渐分别出现。
随着糖尿病性心肌病的进展，钙火花呈现出时间依赖性衰减，这可能部分导致心脏功能障碍。这种异常可能归因于一些钙相关蛋白表达的改变。
