Zhao Limei, Wang Yan, Ma Xiaozhen, Wang Yawen, Deng Xiuling
Department of Physiology and Pathophysiology, Xi'an Jiaotong University College of Medicine, Xi'an, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2013 Jul;33(7):939-44.
To investigate the role of oxidative stress in impaired intermediate-conductance Ca(2+)-activated potassium channels (IKCa)- and small-conductance Ca(2+)-activated potassium channels (SKCa)-mediated relaxation in diabetic resistance arteries.
Rat diabetic model was induced by a high fat and high glucose diet and streptozotocin (STZ) injection. Endothelial function of mesenteric arteries was assessed with the use of wire myography. The expression levels of IKCa and SKCa in cultured human umbilical vein endothelial cells (HUVECs) treated with H2O2 and/or antioxidant alpha lipoic acid (ALA) were measured using Western blotting.
IKCa- and SKCa-mediated vasodilatation in response to acetylcholine was impaired in the third-order mesenteric arterioles of diabetic rats. In cultured HUVECs, H2O2 significantly decreased the protein expression of IKCa and SKCa. ALA alleviated the impairment of both vasodilatation function of the mesenteric arterioles ex vivo and enhanced the expression of IKCa and SKCa challenged with H2O2 in cultured HUVECs.
Our data demonstrated for the first time that impaired IKCa- and SKCa-mediated vasodilatation in diabetes was induced, at least in part, by oxidative stress via down-regulation of IKCa and SKCa channels.
探讨氧化应激在糖尿病抵抗动脉中中间电导钙激活钾通道（IKCa）和小电导钙激活钾通道（SKCa）介导的舒张功能受损中的作用。
通过高脂高糖饮食和注射链脲佐菌素（STZ）诱导大鼠糖尿病模型。使用线式肌张力测定法评估肠系膜动脉的内皮功能。采用蛋白质印迹法检测用H2O2和/或抗氧化剂α硫辛酸（ALA）处理的培养人脐静脉内皮细胞（HUVECs）中IKCa和SKCa的表达水平。
糖尿病大鼠三级肠系膜小动脉中，IKCa和SKCa介导的对乙酰胆碱的血管舒张反应受损。在培养的HUVECs中，H2O2显著降低IKCa和SKCa的蛋白表达。ALA减轻了离体肠系膜小动脉舒张功能的损伤，并增强了培养的HUVECs中受H2O2刺激的IKCa和SKCa的表达。
我们的数据首次证明，糖尿病中IKCa和SKCa介导的血管舒张功能受损至少部分是由氧化应激通过下调IKCa和SKCa通道引起的。
