钙/钙调素依赖性蛋白激酶Ⅱ抑制剂对心房肌细胞钙超载的影响  

Impact of calcium/calmodulin dependent protein kinase Ⅱ inhibitors on calcium overloading of atrial myocardium

作　　者：岑运光[1] 陈相健[2] 

机构地区：[1]海南省人民医院医疗保健中心,海南海口570311 [2]南京医科大学第二附属医院心内科,江苏南京210029

出　　处：《中国生化药物杂志》2014年第5期8-11,15,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金(81170220)

摘　　要：目的探讨钙/钙调素依赖性蛋白激酶Ⅱ(calmodulin-dependent protein kinase Ⅱ,CaMK Ⅱ)抑制剂KN93对大鼠心肌细胞钙超载及CaMK Ⅱ蛋白表达的影响。方法培养大鼠心房肌细胞原代细胞,应用钙离子导入剂ionomycin(1.0μmol/L)诱导心肌钙超载模型,KN93(0.25、0.5、1.0μmo/L)作用下,Fluo-3/AM负载心房肌细胞,激光共聚焦显微镜观察心房肌细胞的收缩频率及细胞游离[Ca2+]i的动态变化,计算平均钙瞬变幅度;采用Western blot法检测CaMKⅡ表达水平。结果 KN93可抑制ionomycin诱导的心肌细胞钙超载,且其抑制率与KN93呈剂量依赖关系,KN93可使心房肌细胞CaMKⅡ表达下降。结论 CaMK Ⅱ抑制剂KN93可纠正ionomycin诱发的大鼠心房肌细胞的钙超载,并下调细胞CaMKⅡ表达水平。Objective To investigate the impact of calcium/calmodulin dependent protein kinase Ⅱ(CaMK Ⅱ) inhibitors KN93 on calcium overloading of atrial myocardium and the influence of CaMKII protein expression. Methods The primitive cells of atrial myocyte were developed,the calcium overload model was induced by ionomycin(1. 0 umol /L),with KN93(0. 25,0. 5,1. 0 μmo /L),atrial myocardium were loaded by Fluo-3 /AM,the intracellular free [Ca2 +]i,atrial myocyte contraction frequency were dynamic observed by laser confocal microscope; the expression of CaMKⅡ was detected by Western blot. Results KN93 can suppress the calcium overload of atrial myocardium induced by ionomycin,and the inhibition rate shows the dose-response relationship,KN93 can downregulate atrial myocardium CaMK Ⅱ expression. Conclusion CaMK Ⅱ inhibitors(KN93) can reduce calcium overloading of cardiomyocytes induced by ionomycin,and downregulate the expression of CaMK Ⅱ.

关 键 词：钙/钙调素依赖性蛋白激酶Ⅱ抑制剂 心房肌细胞 钙超载 

分 类 号：R453.9[医药卫生—治疗学]