南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (07): 939-.

• •    下一篇

Oxidative stress impairs IKCa- and SKCa-mediated vasodilatation in mesenteric arteries from diabetic rats

赵丽梅，王燕，马晓真，王亚文，邓秀玲   

  • 出版日期:2013-07-20 发布日期:2013-07-20

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

  • Online:2013-07-20 Published:2013-07-20

PDF

2539

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。

Abstract: Objective To investigate the role of oxidative stress in impaired intermediate-conductance Ca2 +-activated potassium
channels (IKCa)- and small-conductance Ca2 +-activated potassium channels (SKCa)-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 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. Results 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. Conclusion 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.