Research Institute of Pharmaceutical Sciences, Musashino University, Nishitokyo, Tokyo 202-8585, Japan.
Biol Pharm Bull. 2010;33(6):998-1003. doi: 10.1248/bpb.33.998.
Diabetes mellitus is a well known and important risk factor for cardiovascular diseases, including heart failure. A new model of Type 2 diabetes, Tsumura Suzuki Obese Diabetes (TSOD) mice, was introduced recently into the research field of diabetes. The cardiac functions of TSOD mice were studied in comparison with Tsumura Suzuki Non Obesity (TSNO, non-diabetic control) mice, for the first time. In vivo cardiovascular functions were measured by echocardiography and cardiac catheterization at 7, 12 and 18 months old. TSOD mice had no deterioration of cardiac function despite the long-term persistence of severe obesity, hyperglycemia, hyperinsulinemia and hyperlipidemia, including high density lipoprotein (HDL)-cholesterol. No histopathological abnormalities were observed in the heart of TSOD mice, while several histological abnormalities were observed in the pancreas and kidney of TSOD mice. To investigate vascular endothelium function at 7 months old, intravenous injection of acetylcholine (ACh; 1, 3, 10 microg/kg)- and N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg)-induced mean blood pressure (BP) changes were used. ACh decreased whereas L-NAME increased BP, and no significant differences in BP changes were observed between TSOD and TSNO mice. Moreover, ACh-induced relaxation of the thoracic aortae isolated from TSOD and TSNO mice with intact endothelium were not significantly different. These findings suggest that vascular endothelial cells in TSOD mice are not impaired. It was clearly demonstrated that despite obvious diabetes, cardiac functions of TSOD mice were not impaired even at 18 months old.
糖尿病是一种众所周知的重要心血管疾病风险因素，包括心力衰竭。最近，一种新的 2 型糖尿病模型，Tsumura Suzuki 肥胖糖尿病（TSOD）小鼠，被引入到糖尿病研究领域。首次研究了 TSOD 小鼠与 Tsumura Suzuki 非肥胖（TSNO，非糖尿病对照）小鼠的心脏功能。通过超声心动图和心导管术在 7、12 和 18 个月大时测量体内心血管功能。尽管长期存在严重肥胖、高血糖、高胰岛素血症和高血脂症，包括高密度脂蛋白（HDL）-胆固醇，TSOD 小鼠的心脏功能没有恶化。在 TSOD 小鼠的心脏中没有观察到组织病理学异常，而在 TSOD 小鼠的胰腺和肾脏中观察到了几种组织学异常。为了研究 7 个月大时的血管内皮功能，静脉注射乙酰胆碱（ACh；1、3、10 μg/kg）和 N(G)-硝基-L-精氨酸甲酯（L-NAME；50 mg/kg）诱导的平均血压（BP）变化。ACh 降低而 L-NAME 增加 BP，TSOD 和 TSNO 小鼠之间的 BP 变化没有显著差异。此外，来自 TSOD 和 TSNO 小鼠的具有完整内皮的胸主动脉对 ACh 诱导的松弛作用没有显著差异。这些发现表明 TSOD 小鼠的血管内皮细胞没有受损。研究清楚地表明，尽管存在明显的糖尿病，但 TSOD 小鼠的心脏功能甚至在 18 个月大时也没有受损。
