Mizushige K, Yao L, Noma T, Kiyomoto H, Yu Y, Hosomi N, Ohmori K, Matsuo H
Second Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan.
Circulation. 2000 Feb 29;101(8):899-907. doi: 10.1161/01.cir.101.8.899.
Considerable controversy exists regarding impairment of cardiac function in diabetes mellitus (DM). We investigated the serial changes in left ventricular (LV) histopathology and LV filling dynamics in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of type II DM.
In 54 OLETF and 54 non-DM rats, body weight, blood pressure, heart rate, and transmitral pulsed Doppler examinations were performed from 5 to 47 weeks of age. An oral glucose tolerance test was performed at 10, 20, and 30 weeks of age. The hearts were excised for histopathology, including immunohistochemistry and histomorphometry of collagen, and measurement of hydroxyproline at baseline and each stage of developing DM. In the prediabetic stage (15 weeks of age), in which fast blood glucose remained normal, OLETF rats manifested mild obesity, postprandial hyperglycemia, and hyperinsulinemia, and early diastolic transmitral inflow exhibited prolonged deceleration time (OLETF, 59+/-10 ms versus non-DM, 49+/-8 ms, P<0.01) and low peak velocity (OLETF, 73+/-11 cm/s versus non-DM, 88+/-11 cm/s, P<0.01). Histopathology revealed extracellular fibrosis and abundant transforming growth factor-beta(1) receptor II in LV myocytes of OLETF rats. At 15 weeks of age, the ratio of collagen area/visual field of LV wall in OLETF rats (8.3+/-1.3%) was larger than that in non-DM rats (4.9+/-1.8%, P<0.0001), and the collagen content/dry tissue weight ratio of heart was significantly higher in OLETF (2. 0+/-0.5 mg/g) than non-DM (1.3+/-0.2 mg/g, P<0.01) rats.
A metabolic abnormality present in the prestage of type II DM may produce LV fibrosis and alteration in cardiac function.
关于糖尿病（DM）患者心脏功能受损存在相当大的争议。我们研究了大冢长-艾氏-德岛肥胖（OLETF）大鼠左心室（LV）组织病理学和左心室充盈动力学的系列变化，该大鼠已被确立为II型糖尿病的动物模型。
对54只OLETF大鼠和54只非糖尿病大鼠，在5至47周龄期间进行体重、血压、心率和经二尖瓣脉冲多普勒检查。在10、20和30周龄时进行口服葡萄糖耐量试验。在基线和糖尿病发展的每个阶段，取出心脏进行组织病理学检查，包括胶原蛋白的免疫组织化学和组织形态计量学，以及羟脯氨酸的测量。在糖尿病前期阶段（15周龄），空腹血糖仍正常，OLETF大鼠表现为轻度肥胖、餐后高血糖和高胰岛素血症，早期舒张期经二尖瓣血流表现为减速时间延长（OLETF，59±10毫秒对非糖尿病大鼠，49±8毫秒，P<0.01）和峰值速度降低（OLETF，73±11厘米/秒对非糖尿病大鼠，88±11厘米/秒）。组织病理学显示OLETF大鼠左心室心肌细胞存在细胞外纤维化和丰富的转化生长因子-β(1)受体II。15周龄时，OLETF大鼠左心室壁胶原面积/视野比（8.3±1.3%）大于非糖尿病大鼠（4.9±1.8%，P<0.0001），OLETF大鼠心脏的胶原含量/干组织重量比（2.0±0.5毫克/克）显著高于非糖尿病大鼠（1.3±0.2毫克/克）。
II型糖尿病前期存在的代谢异常可能导致左心室纤维化和心脏功能改变。
