炎症病理情况下阿托伐他汀对大鼠主动脉平滑肌细胞膜电位影响及其可能机制研究  

The effect and mechanism of atorvastatin on the membrane potential （MP） and BKCa in rat aorta smooth muscle cells in inflammation

作　　者：吴桂平[1] 张彦红[1] 杨滢[1] 周瀛[1] 邹慕蔚[1] 曲晓婷[1] 李颖[1] 付鑫[1] 

机构地区：[1]沈阳医学院沈洲医院心内科,辽宁省110002

出　　处：《中国心血管病研究》2013年第8期615-619,共5页Chinese Journal of Cardiovascular Research

基　　金：辽宁省科学计划项目资助（编号2011225032）;辽宁省教育厅科研课题资助（编号L2010550）

摘　　要：目的研究炎症病理情况下阿托伐他汀对大鼠主动脉平滑肌细胞膜电位及大电导钙敏感钾通道活性的影响。方法通过激光共聚焦显微镜检测DIBAC4（3）标记的大鼠主动脉平滑肌细胞（AsMc）膜电位，观察-＋／-catalase（过氧化氢清除剂）时IL-1β与ASMCs共培养后，阿托伐他汀对膜电位的影响，探讨阿托伐他汀能否逆转IL-1β对血管平滑肌细胞膜电位的影响及其可能机制，以及在炎症情况下阿托伐他汀对BKca单通道活性的影响。结果12h50ng／mlIL-1β的处理使ASMCs细胞膜去极化，100μmol／L阿托伐他汀可以逆转IL-1β引起的ASMCs去极化；12h50ng／mlIL-1β的处理抑制ASMCs细胞膜上BKca通道活性，而100umol／L阿托伐他汀可以逆转IL-1β对BKca通道活性的影响。结论阿托伐他汀可以完全逆转IL-1β引起的ASMCs去极化，BKca通道是形成血管平滑肌细胞膜电位的重要原因。膜电位与心血管疾病密切相关，BKca通道可能是心血管疾病新的药物靶点，阿托伐他汀可能成为直接开放血管平滑肌细胞BKca通道新的药物。Objective The aim of our study was to investigate the effect of atorvastatin on the Membrane potential （MP）and BKCa in rat aorta smooth muscle cells（ASMCs） in inflammation treated with IL-113. Methods The effects of atorvastatin on MP of ASMCs treated with 50 ng/ml IL-I[3 for 12 hours in the present or absence of catalase , the MP was determined by the intensity of DiBAC4 （3） detected under confocal microscope. To test whether atorvastatin affects single BK channel activity of ASMCs treated with 5ng/ml IL-113 for 12 hours, inside- out patch clamping was used to test. Results 50 ng/ml IL-I[3 significantly depolarizarized ASMCs when applied 12 hours. And 100 Ixmol atorvastatin could not only block the IL-I[3 induced depolarization, but also hyperpolar- ized the MP to some extent BK channel activity was significantly suppressed when 12h treatment of 50 ng/ml IL-I~ while 100 p, mol/L atorvastatin completely abolished the effect. Conclusion 50 ng/ml IL-113 significantly depo- larizarized ASMCs when applied 12 hours, and 100 ~mol/L atorvastatin could block the IL-113 induced depolar- ization. The critical influence of BK channel in ASMCs suggests an involvement in cardiovascular diseases. Atorvas- tatin could act as a BK opener and an effective therapeutic agents. And because of it＇s widely accepted safety and well tolerated, atorvastatin has the broad prospects in dealing with BK channel associated vascular dysfunction.

关 键 词：阿托伐他汀 BK通道 白介素1Β 平滑肌细胞 膜电位 膜片钳 

分 类 号：R589[医药卫生—内分泌]