Hamblin Milton, Smith Holly M, Hill Michael F
Department of Biomedical Sciences, Division of Cardiovascular Biology, Meharry Medical College, Nashville, Tennessee, USA.
J Card Fail. 2007 Dec;13(10):884-92. doi: 10.1016/j.cardfail.2007.07.002.
Diabetic cardiomyopathy has been documented as an underlying cause of heart failure in diabetic patients. Although oxidative stress has been implicated in diabetic cardiomyopathy, much of the current evidence lacks specificity. Furthermore, studies investigating antioxidant protection with vitamin E in this unique cardiac phenomenon have yet to be performed. In the present study, we sought to determine whether vitamin E supplementation can confer cardioprotective effects against diabetic cardiomyopathy in relation to specific and quantitative markers of myocardial oxidative stress.
Diabetes was induced in rats by a single injection of streptozotocin. Animals were fed either a basal diet or a diet enriched with 2000 IU of vitamin E per kilogram beginning immediately after induction of diabetes and continued for 8 weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) hemodynamic analysis. Myocardial oxidative stress was assessed by measuring the formation of 8-iso-prostaglandin F2alpha and oxidized glutathione. In the unsupplemented streptozotocin-diabetic rats, LV systolic pressure, rate of pressure increase (+dP/dt), and rate of pressure decay (-dP/dt) were depressed, whereas LV end-diastolic pressure was increased, indicating reduced LV contractility and slowing of LV relaxation. These hemodynamic alterations were accompanied by increased myocardial formation of 8-iso-prostaglandin F2alpha and oxidized glutathione. Vitamin E supplementation improved LV function and significantly attenuated myocardial 8-iso-prostaglandin F2alpha and oxidized glutathione accumulation in streptozotocin-diabetic rats.
These findings demonstrate the usefulness of vitamin E supplementation during the early phases of type I diabetes for the prophylaxis of cardiomyopathy and subsequent heart failure.
糖尿病性心肌病已被证明是糖尿病患者心力衰竭的潜在病因。尽管氧化应激与糖尿病性心肌病有关，但目前的许多证据缺乏特异性。此外，尚未有研究探讨维生素E对这种独特心脏现象的抗氧化保护作用。在本研究中，我们试图确定补充维生素E是否能针对心肌氧化应激的特定和定量标志物，对糖尿病性心肌病发挥心脏保护作用。
通过单次注射链脲佐菌素诱导大鼠患糖尿病。自糖尿病诱导后立即开始，动物分别喂食基础饮食或每千克富含2000国际单位维生素E的饮食，并持续8周。通过左心室（LV）血流动力学分析检查大鼠是否患有糖尿病性心肌病。通过测量8-异前列腺素F2α和氧化型谷胱甘肽的形成来评估心肌氧化应激。在未补充维生素E的链脲佐菌素诱导的糖尿病大鼠中，左心室收缩压、压力上升速率（+dP/dt）和压力下降速率（-dP/dt）降低，而左心室舒张末期压力升高，表明左心室收缩力降低和左心室舒张减慢。这些血流动力学改变伴随着心肌中8-异前列腺素F2α和氧化型谷胱甘肽形成增加。补充维生素E改善了链脲佐菌素诱导的糖尿病大鼠的左心室功能，并显著减轻了心肌中8-异前列腺素F2α和氧化型谷胱甘肽的蓄积。
这些发现表明，在I型糖尿病早期补充维生素E对预防心肌病及随后的心力衰竭有用。
