Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM U1055, Université Joseph Fourier, BP 53, Grenoble cedex 09 F-38041, France.
Cardiovasc Diabetol. 2013 Mar 25;12:49. doi: 10.1186/1475-2840-12-49.
There has been accumulating evidence associating diabetes mellitus and cardiovascular dysfunctions. However, most of the studies are focused on the late stages of diabetes and on the function of large arteries. This study aimed at characterizing the effects of the early phase of diabetes mellitus on the cardiac and vascular function with focus on the intact coronary microvasculature and the oxidative stress involved.
Zucker diabetic fatty rats and their lean littermates fed with standard diet A04 (Safe) were studied at the 11th week of age. Biochemical parameters such as glucose, insulin and triglycerides levels as well as their oxidative stress status were measured. Their hearts were perfused ex vivo according to Langendorff and their cardiac activity and coronary microvascular reactivity were evaluated.
Zucker fatty rats already exhibited a diabetic state at this age as demonstrated by the elevated levels of plasma glucose, insulin, glycated hemoglobin and triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac mechanical function and coronary flow. This was accompanied by an increase in the overall oxidative stress of the organs. However, estimation of the active form of endothelial nitric oxide synthase and coronary reactivity indicated a preserved function of the coronary microvessels at this phase of the disease. Diabetes affected also the cardiac membrane phospholipid fatty acid composition by increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels.
The presence of diabetes, even at its beginning, significantly increased the overall oxidative stress of the organs resulting to decreased cardiac mechanical activity ex vivo. However, adaptations were adopted at this early phase of the disease regarding the preserved coronary microvascular reactivity and the associated cardiac phospholipid composition in order to provide a certain protection to the heart.
越来越多的证据表明糖尿病与心血管功能障碍有关。然而，大多数研究都集中在糖尿病的晚期和大动脉的功能上。本研究旨在描述糖尿病早期对心脏和血管功能的影响，重点关注完整的冠状动脉微血管和涉及的氧化应激。
11 周龄时，研究了喂食标准饮食 A04（Safe）的 Zucker 糖尿病肥胖大鼠及其瘦型同窝仔鼠。测量了葡萄糖、胰岛素和甘油三酯等生化参数以及它们的氧化应激状态。根据 Langendorff 方案对它们的心脏进行离体灌注，并评估其心脏活动和冠状动脉微血管反应性。
肥胖 Zucker 大鼠在这个年龄已经表现出糖尿病状态，血浆葡萄糖、胰岛素、糖化血红蛋白和甘油三酯水平升高。离体灌注其心脏显示心脏机械功能和冠状动脉流量降低。这伴随着器官整体氧化应激的增加。然而，内皮型一氧化氮合酶的活性形式和冠状动脉反应性的估计表明，在疾病的这个阶段，冠状动脉微血管的功能仍然存在。糖尿病还通过增加花生四烯酸和 n-3 多不饱和脂肪酸的水平，影响心脏膜磷脂脂肪酸组成。
即使在疾病的早期，糖尿病的存在也会显著增加器官的整体氧化应激，导致离体心脏机械活动降低。然而，在疾病的早期阶段，已经采取了适应措施，以保持冠状动脉微血管反应性和相关的心脏磷脂组成，从而为心脏提供一定的保护。
