氧化应激损伤中电导和小电导钙激活钾通道介导的糖尿病大鼠肠系膜动脉舒张  

Oxidative stress impairs IK_(Ca-) and SK_(Ca-) mediated vasodilatation in mesenteric arteries from diabetic rats

作　　者：赵丽梅[1] 王燕[1] 马晓真[1] 王亚文[1] 邓秀玲[1] 

机构地区：[1]西安交通大学医学院生理学与病理生理学系,陕西西安710061

出　　处：《南方医科大学学报》2013年第7期939-944,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(81100231,81070129,81200097);陕西省自然科学基金(2011JQ4021)~~

摘　　要：目的探讨氧化应激在糖尿病阻力血管中电导钙激活钾通道(intermediate-conductance Ca2+-activated potassium channels,IKCa)和小电导钙激活钾通道(small-conductance Ca2+-activated potassium channels,SKCa)介导的内皮舒张功能障碍中的作用。方法采用高糖高脂饲料喂养联合链脲佐菌素注射建立糖尿病大鼠模型。采用离体血管张力实验观察大鼠肠系膜三级动脉内皮介导的舒张功能变化,Western blotting观察IKCa和SKCa的表达变化。结果 IKCa和SKCa介导的糖尿病大鼠肠系膜三级动脉舒张功能减弱,H2O2显著降低培养的人脐静脉内皮细胞IKCa和SKCa的表达,抗氧化剂α-硫辛酸(alpha lipoic acid,ALA)在体给药和体外孵育细胞可部分纠正IKCa和SKCa功能的损伤及表达的下调。结论糖尿病状态下氧化应激通过下调内皮细胞IKCa和SKCa表达而损伤IKCa和SKCa介导的血管舒张功能。Objective To investigate the role of oxidative stress in impaired intermediate-conductance Ca 2 ＋ -activated potassium channels （IK Ca ）- and small- conductance Ca 2 ＋ - activated potassium channels （SK Ca ）- mediated relaxation in diabetic resistance arteries. Methods 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 IK Ca and SK Ca in cultured human umbilical vein endothelial cells （HUVECs） treated with H 2 O 2 and/or antioxidant alpha lipoic acid （ALA） were measured using Western blotting. Results IK Ca - and SK Ca - mediated vasodilatation in response to acetylcholine was impaired in the third-order mesenteric arterioles of diabetic rats. In cultured HUVECs, H 2 O 2 significantly decreased the protein expression of IK Ca and SK Ca . ALA alleviated the impairment of both vasodilatation function of the mesenteric arterioles ex vivo and enhanced the expression of IK Ca and SK Ca challenged with H 2 O 2 in cultured HUVECs. Conclusion Our data demonstrated for the first time that impaired IK Ca - and SK Ca -mediated vasodilatation in diabetes was induced, at least in part, by oxidative stress via down-regulation of IK Ca and SK Ca channels.

关 键 词：糖尿病 钙激活钾通道 氧化应激 内皮细胞 

分 类 号：R587.1[医药卫生—内分泌]