外源性磷酸肌酸对缺血豚鼠心室肌细胞钠通道的影响  

Effect of Exogenous Phosphocreatine on Natrium Current in Ischemic Ventricular Myocytes of Guinea Pig

作　　者：时向民[1] 李天德[2] 王玉堂[2] 单兆亮[2] 杨庭树[2] 

机构地区：[1]解放军总医院海南分院心内科,海南三亚572000 [2]解放军总医院心内科,北京100853

出　　处：《中国现代应用药学》2014年第1期13-17,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：解放军总医院苗圃基金(08MP13)

摘　　要：目的：观察不同浓度外源性磷酸肌酸（exogenous phosphocreatine, PCr）对豚鼠缺血心室肌细胞钠通道（INa）电流的影响,探讨其预防缺血性心律失常的电生理学机制。方法：心室肌细胞经酶解从豚鼠左心室获得,膜片钳全细胞模式记录INa电流,通过灌注模拟缺血液并充以95%N2 5%CO2的混合气体建立缺血模型,将PCr加入模拟缺血液中分别配成5, 10, 20,30 mmol/L浓度。将细胞分成6组,分别予模拟缺血液,含有5, 10, 20,30mmol/L浓度PCr的模拟缺血液,台氏液灌流,后者充以95%O2 5%CO2的混合气体。10min后记录各组的峰电流及电流密度。结果：与台氏液组相比,单纯模拟缺血液组INa峰电流密度降低80.1？2.5%（p〈0.05）,含有5, 10, 20, 30mmol/L浓度PCr的模拟缺血液组INa峰电流密度分别降低56.2？4.6%（p〈0.05）；30.3？5.3%（p〈0.05）；39.0？5.5%（p〈0.05）；42.6？4.8%（p〈0.05）。10与5, 20, 30mmol/L之间具有统计学差异（p〈0.05）。结论： PCr能增加缺血时受抑制的INa峰电流及电流密度,这可能是其预防缺血性心律失常的电生理学机制。PCr在低浓度 （0~10mmol/L）对INa峰电流及电流密度的影响呈现明显的量效关系。Objective： The aim of this study is to determine the effect of exogenous phosphocreatine（PCr） with different concentration on natrium （ INa ） current in guinea pig ischemic ventricular myocytes and to explore the antiarrhythmia mechanism in the treatment of ischemic heart disease. Methods： Ventricular myocytes were isolated enzymatically from left ventricular of guinea pig. Peak INacurrent was recorded using patch clamp techniques in the whole-cell configuration when myocytes had been superfused with normal Tyrode solution, simple ischemic solution, ischemic solution containing PCr with different concentration of 5, 10, 20, 30 mmol/L for 10 minutes respectively. Results： Peak INa current density of myocytes superfused with simple simulated ischemic solution was significantly reduced by 80.1？2.5%（p〈0.05）compared with myocytes superfused with normal Tyrode solution. Ischemic solution containing PCr of 5, 10, 20, 30mmol/L reduced peak INa current density by 56.2？4.6%（p〈0.05）;30.3？5.3%（p〈0.05）;39.0？5.5%（p〈0.05）;42.6？4.8%（p〈0.05）respectively. There was Statistical significance among ischemic solution containing PCr of 10 and 5, 20, 30 mmol/L（p〈0.05）.Conclusion： PCr could reverse the inhibition of INacurrent under ischemic condition, which could be the mechanism responsible for arrhythmia prevention in ischemia heart disease. 0~10mmol/L PCr exerted significant dose-effect relationship and concentration more than 10mmol/L could slightly decrease INa current density.

关 键 词：磷酸肌酸 钠电流 缺血性心律失常 膜片钳 

分 类 号：R966[医药卫生—药理学]