Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, 2176 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3 Canada.
Eur J Pharmacol. 2010 Sep 10;642(1-3):128-33. doi: 10.1016/j.ejphar.2010.06.009. Epub 2010 Jun 12.
Diabetes is associated with metabolic and vascular abnormalities. We investigated if arterial and venous constrictions are impaired in rat models of diabetes. Wistar rats (5 weeks old) were fed a normal or high-fructose diet (60% of caloric intake). On Day 14, half of the animals in each diet regimen were given streptozotocin (60 mg/kg, i.v.). On Day 35, plasma insulin and triglyceride were measured, and on Day 42, insulin sensitivity (via hyperinsulinemic euglycemic clamp), and pressor as well as mean circulatory filling pressure (index of venous tone) responses to noradrenaline were determined. The rats treated with streptozotocin or fructose-streptozotocin were hyperglycemic, hypoinsulinemic and insulin resistant, and they also had reduced potency (increased ED(50)) of pressor response and reduced venoconstriction to noradrenaline compared to the two groups not given streptozotocin. Plasma triglyceride was unchanged in streptozotocin-treated rats, moderately increased in fructose-fed rats, and markedly increased in fructose-streptozotocin-treated rats. Hyperglycemia, insulin resistance and alpha-adrenoceptor-mediated venous contractile dysfunction were more pronounced in the group given fructose-streptozotocin than that given streptozotocin alone. The presence of marked hypertriglyceridemia, insulin resistance and vascular dysfunction makes the fructose-streptozotocin-treated rats a suitable model for study of metabolic and vascular abnormalities in advanced type 2 diabetes.
糖尿病与代谢和血管异常有关。我们研究了糖尿病大鼠模型中动脉和静脉收缩是否受损。Wistar 大鼠（5 周龄）喂食正常或高果糖饮食（热量摄入的 60%）。在第 14 天，每种饮食方案的一半动物给予链脲佐菌素（60mg/kg，iv）。在第 35 天，测量血浆胰岛素和甘油三酯，在第 42 天，测定胰岛素敏感性（通过高胰岛素正常血糖钳夹）以及去甲肾上腺素的升压和平均循环充盈压（静脉张力指数）反应。用链脲佐菌素或果糖-链脲佐菌素处理的大鼠血糖升高，胰岛素水平降低，胰岛素抵抗，且其升压反应的效力降低（ED50 增加），对去甲肾上腺素的静脉收缩反应降低，与未用链脲佐菌素处理的两组相比。血浆甘油三酯在链脲佐菌素处理的大鼠中不变，在果糖喂养的大鼠中中度增加，在果糖-链脲佐菌素处理的大鼠中明显增加。在给予果糖-链脲佐菌素的大鼠中，高血糖、胰岛素抵抗和α-肾上腺素能受体介导的静脉收缩功能障碍比单独给予链脲佐菌素的大鼠更为明显。明显的高甘油三酯血症、胰岛素抵抗和血管功能障碍的存在使果糖-链脲佐菌素处理的大鼠成为研究 2 型糖尿病晚期代谢和血管异常的合适模型。
