ABSTRACT

We used a type 2 diabetes rat model produced by a high fat diet (HFD) followed by low dose streptozotocin (STZ) to study diabetic vasculopathy. Animals were evaluated for early vascular structural changes, endothelial function, inflammation, lipid profile and oxidative stress. We used 20 male Sprague-Dawley rats divided equally into control and diabetic groups. Diabetic rats were fed an HFD for 4 weeks, injected intraperitoneally with STZ, then sacrificed at week 15. Aortic endothelial nitric oxide synthase (eNOS), aortic superoxide dismutase (SOD), endothelial-dependent and independent relaxation and contraction, intima-media thickness (IMT), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were measured. Histopathological characteristics also were assessed. Diabetic rats exhibited higher fasting blood glucose (FBG), low density lipoprotein, total cholesterol and triglycerides compared to the control group. Aortic endothelium-dependent relaxation due to acetylcholine (ACh) was lower, while aortic endothelium-dependent contraction due to calcium ionophore and endothelium-independent contraction due to phenylephrine (PE) were higher for the diabetic group. eNOS expression was lower in the diabetic group compared to controls. IMT and MDA levels were increased, while SOD activity was decreased in the diabetic group compared to controls. TNF-α was higher in the diabetic group than for controls. Our type 2 diabetes model exhibited endothelial dysfunction associated with early vascular structural changes, dyslipidemia, increased vascular oxidative stress, and inflammation. Therefore, the model is suitable for studying diabetic atherosclerosis.

摘要

我们使用由高脂肪饮食 (HFD) 和低剂量链脲佐菌素 (STZ) 产生的 2 型糖尿病大鼠模型来研究糖尿病血管病变。评估动物的早期血管结构变化、内皮功能、炎症、脂质谱和氧化应激。我们使用了 20 只雄性 Sprague-Dawley 大鼠，平均分为对照组和糖尿病组。糖尿病大鼠喂食 HFD 4 周，腹腔注射 STZ，然后在第 15 周处死。 主动脉内皮一氧化氮合酶 (eNOS)、主动脉超氧化物歧化酶 (SOD)、内皮依赖性和独立的舒张和收缩、内膜中层厚度(IMT)、丙二醛 (MDA) 和肿瘤坏死因子-α (TNF-α) 进行了测量。还评估了组织病理学特征。糖尿病大鼠表现出较高的空腹血糖（FBG），与对照组相比，低密度脂蛋白、总胆固醇和甘油三酯。糖尿病组由于乙酰胆碱 (ACh) 引起的主动脉内皮依赖性舒张较低，而钙离子载体引起的主动脉内皮依赖性收缩和去氧肾上腺素 (PE) 引起的主动脉内皮依赖性收缩较高。与对照组相比，糖尿病组的 eNOS 表达较低。与对照组相比，糖尿病组的 IMT 和 MDA 水平增加，而 SOD 活性降低。糖尿病组的 TNF-α 高于对照组。我们的 2 型糖尿病模型表现出与早期血管结构变化、血脂异常、血管氧化应激增加和炎症相关的内皮功能障碍。因此，该模型适用于研究糖尿病动脉粥样硬化。与对照组相比，总胆固醇和甘油三酯。对于糖尿病组，乙酰胆碱 (ACh) 引起的主动脉内皮依赖性舒张较低，而钙离子载体引起的主动脉内皮依赖性收缩和去氧肾上腺素 (PE) 引起的主动脉内皮依赖性收缩较高。与对照组相比，糖尿病组的 eNOS 表达较低。与对照组相比，糖尿病组的 IMT 和 MDA 水平增加，而 SOD 活性降低。糖尿病组的 TNF-α 高于对照组。我们的 2 型糖尿病模型表现出与早期血管结构变化、血脂异常、血管氧化应激增加和炎症相关的内皮功能障碍。因此，该模型适用于研究糖尿病动脉粥样硬化。与对照组相比，总胆固醇和甘油三酯。糖尿病组由于乙酰胆碱 (ACh) 引起的主动脉内皮依赖性舒张较低，而钙离子载体引起的主动脉内皮依赖性收缩和去氧肾上腺素 (PE) 引起的主动脉内皮依赖性收缩较高。与对照组相比，糖尿病组的 eNOS 表达较低。与对照组相比，糖尿病组的 IMT 和 MDA 水平增加，而 SOD 活性降低。糖尿病组的 TNF-α 高于对照组。我们的 2 型糖尿病模型表现出与早期血管结构变化、血脂异常、血管氧化应激增加和炎症相关的内皮功能障碍。因此，该模型适用于研究糖尿病动脉粥样硬化。