VanGilder R L, Kelly K A, Chua M D, Ptachcinski R L, Huber Jason D
Department of Basic Pharmaceutical Sciences, West Virginia University, P.O. Box 9530, Morgantown, WV 26506, USA.
Exp Brain Res. 2009 Jul;197(1):23-34. doi: 10.1007/s00221-009-1866-6. Epub 2009 Jun 30.
Uncontrolled or poorly controlled blood glucose during diabetes is an important factor in worsened vascular function. While evidence suggests that hyperglycemia-induced oxidative stress plays a prominent role in development of microangiopathy of the retina, kidney, and nerves, the role oxidative stress plays on blood-brain barrier (BBB) function and structure has lagged behind. In this study, a natural antioxidant, sesamol, was administered to streptozotocin (STZ)-induced diabetic rats to examine the role that oxidative stress plays on BBB structure and function. Experiments were conducted at 56 days after STZ injection. Male Sprague-Dawley rats randomly were divided into four treatment groups CON--control; STZ--STZ-induced diabetes; CON + S--control + sesamol; STZ + S--STZ-induced diabetes + sesamol. Functional and structural changes to the BBB were measured by in situ brain perfusion and western blot analysis of changes in tight junction protein expression. Oxidative stress markers were visualized by fluorescent confocal microscopy and assayed by spectrophotometric analysis. Results demonstrated that the increased BBB permeability observed in STZ-induced diabetic rats was attenuated in STZ + S rats to levels observed in CON. Sesamol treatment reduced the negative impact of STZ-induced diabetes on tight junction protein expression in isolated cerebral microvessels. Oxidative stress markers were elevated in STZ as compared to CON. STZ + S displayed an improved antioxidant capacity which led to a reduced expression of superoxide and peroxynitrite and reduced lipid peroxidation. In conclusion, this study showed that sesamol treatment enhanced antioxidant capacity of the diabetic brain and led to decreased perturbation of hyperglycemia-induced changes in BBB structure and function.
糖尿病期间血糖不受控制或控制不佳是血管功能恶化的一个重要因素。虽然有证据表明高血糖诱导的氧化应激在视网膜、肾脏和神经微血管病变的发展中起主要作用，但氧化应激对血脑屏障（BBB）功能和结构的作用却滞后了。在本研究中，将一种天然抗氧化剂芝麻酚给予链脲佐菌素（STZ）诱导的糖尿病大鼠，以研究氧化应激对血脑屏障结构和功能的作用。实验在注射STZ后56天进行。雄性Sprague-Dawley大鼠随机分为四个治疗组：CON——对照组；STZ——STZ诱导的糖尿病组；CON + S——对照组 + 芝麻酚；STZ + S——STZ诱导的糖尿病 + 芝麻酚组。通过原位脑灌注和紧密连接蛋白表达变化的蛋白质印迹分析来测量血脑屏障的功能和结构变化。通过荧光共聚焦显微镜观察氧化应激标志物，并通过分光光度分析进行测定。结果表明，在STZ诱导的糖尿病大鼠中观察到的血脑屏障通透性增加在STZ + S组大鼠中减弱至CON组观察到的水平。芝麻酚治疗减少了STZ诱导的糖尿病对分离的脑微血管中紧密连接蛋白表达的负面影响。与CON组相比，STZ组的氧化应激标志物升高。STZ + S组显示出改善的抗氧化能力，导致超氧化物和过氧亚硝酸盐的表达降低以及脂质过氧化减少。总之，本研究表明芝麻酚治疗增强了糖尿病脑的抗氧化能力，并导致高血糖诱导的血脑屏障结构和功能变化的扰动减少。
