Privistirescu Andreea I, Sima Alexandra, Duicu Oana M, Timar Romulus, Roșca Mariana G, Sturza Adrian, Muntean Danina M
a Department of Functional Sciences - Pathophysiology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania.
b Department of Internal Medicine II - Diabetes, Nutrition and Metabolic Diseases, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania.
Can J Physiol Pharmacol. 2018 Oct;96(10):1012-1016. doi: 10.1139/cjpp-2018-0119. Epub 2018 Jun 12.
Endothelial dysfunction and the related increase in reactive oxygen species (ROS) production are important events in the pathophysiology of diabetes mellitus (DM). Methylene blue (MB) has been systematically investigated for its protective effects against refractory hypotension and mitochondrial dysfunction. We have previously demonstrated that MB improved mitochondrial respiration and partially decreased oxidative stress in diabetic rat hearts. The present study was aimed to investigate whether MB modulates vascular function and ROS production in thoracic aortic rings isolated from rats with streptozotocin-induced DM (after 4 weeks of hyperglycemia). The effects of MB (0.1 μM, 30 min ex vivo incubation) on vascular reactivity in organ chamber (phenylephrine-induced contraction, acetylcholine-induced relaxation) and HO production (assessed by ferrous iron xylenol orange oxidation assay) were investigated in vascular preparations with intact endothelium and after denudation. DM elicited a significant alteration of vascular function: increased contractility to phenylephrine, attenuation of acetylcholine-dependent relaxation, and augmented HO generation. Ex vivo incubation with MB partially reversed all these changes (by approximately 70%) in vascular segments with intact endothelial layer (but not in denuded vessels). In conclusion, MB might be useful in alleviating endothelial dysfunction and mitigating endothelial oxidative stress, observations that clearly require further investigation in the setting of cardiometabolic disease.
内皮功能障碍以及活性氧（ROS）生成增加是糖尿病（DM）病理生理学中的重要事件。亚甲蓝（MB）已被系统研究其对难治性低血压和线粒体功能障碍的保护作用。我们之前已经证明，MB可改善糖尿病大鼠心脏的线粒体呼吸并部分降低氧化应激。本研究旨在探讨MB是否能调节链脲佐菌素诱导的糖尿病大鼠（高血糖4周后）胸主动脉环的血管功能和ROS生成。研究了MB（0.1 μM，离体孵育30分钟）对完整内皮血管标本和去内皮血管标本中器官浴槽内血管反应性（去氧肾上腺素诱导的收缩、乙酰胆碱诱导的舒张）和HO生成（通过亚铁离子二甲酚橙氧化法评估）的影响。糖尿病引起血管功能的显著改变：对去氧肾上腺素的收缩性增加、乙酰胆碱依赖性舒张减弱以及HO生成增加。用MB离体孵育可部分逆转完整内皮血管段的所有这些变化（约70%）（但在去内皮血管中无此作用）。总之，MB可能有助于减轻内皮功能障碍和缓解内皮氧化应激，这些观察结果显然需要在心脏代谢疾病背景下进一步研究。
