阿托伐他汀对大鼠缺血再灌注左室心肌细胞瞬时钠电流的作用  

Effects of atorvastatin on transient sodium currents in rat left ventricular myocytes suffering from simulated ischemia-reperfusion

作　　者：王芳[1,2] 李洪仕[1] 万征[1] 边波[1] 滕天明[1] 赵青[1] 

机构地区：[1]天津医科大学总医院心血管病中心,300052 [2]天津市第四中心医院神经内科

出　　处：《中华心脏与心律电子杂志》2014年第1期35-38,共4页Chinese Journal of Heart and Heart Rhythm(Electronic Edition)

基　　金：天津市高等学校科技发展基金(20090141)

摘　　要：目的观察阿托伐他汀对大鼠缺血再灌注左室心肌细胞瞬时钠电流(I_(Na))的作用。方法 Wistar大鼠24只,酶解分离存活有效左室心肌细胞23个,随机分为3组,对照组,即单纯细胞缺血模型(再灌注缺血电极外液,n=8),再灌注组(再灌注标准电极外液,n=7)和他汀干预组(再灌注含阿托伐他汀5μmol/L的电极外液,n=8)。3组细胞均置于标准电极外液中记录正常基线I_(Na),此后灌流缺血电极外液,以测定缺血基线I_(Na)(缺血20 min),再行再灌注与干预实验。采用全细胞膜片钳记录I_(Na),计算I/Imax作为标准化I_(Na)。比较3组的标准化I_(Na)(电位-40 mV)、半激活电压(V_(1/2))和激活曲线斜率(k值),采用SPSS 20.0软件统计分析,使用重复测量资料的方差分析。结果(1)正常基线I_(Na),3组间差异无统计学意义。与正常基线I_(Na)相比,在缺血20min时,3组细胞标准化I_(Na)、V_(1/2)和k值均减小(t=2.861、9.462、6.264,均P<0.01),但3组间比较差异无统计学意义。(2)再灌注3 min时,再灌注组I_(Na)(0.83±0.11比0.57±0.09,P<0.01),他汀干预组I_(Na)(0.92±0.04比0.72±0.05,P<0.01)均比缺血基线I_(Na)降低,对照组无变化。再灌注组和他汀干预组I_(Na)均低于对照组,而他汀干预组高于再灌注组(F=23.738,P<0.05)。(3)再灌注3 min时,对照组V_(1/2)和k值和缺血基线比较无差异,再灌注组均增大[V_(1/2)(-58.87±3.36)mV比(-54.33±2.40)mV,k值(1.25±0.59)比(1.91±0.84),t=-3.179、-2.904,均P<0.05],他汀干预组,V_(1/2)增大[(-57.80±2.97)mV比(-52.76±3.14)mV,t=-5.706,P<0.01],k值无变化(P>0.05)。结论大鼠左室心肌细胞I_(Na)在缺血时降低,再灌注时继续降低;阿托伐他汀可部分抑制再灌注引起的I_(Na)减小,并使I_(Na)的激活加快。Objective To observe the effects of atorvastatin on transient sodium currents （ INa ） on ventricular myocytes during ischemia-reperfusion .Methods Twenty-four Wistar rats were used , and the twenty-three effective left ventricular myocytes were successfully isolated , which were randomly divided into 3 groups：control group which was reperfused with ischemia extracellular fluid （ n=8 ） , ischemia-reperfusion group which was reperfused with standard extracellular fluid （ n=7 ） and statin group which was reperfused with standard extracellular fluid containing 5 μmol/L atorvastatin（n=8）.All cells of 3 groups were put in hypoxic and acidic extracellular fluid , standing for 20 min to establish ischemia model .Then, the cells of 3 groups were underwent ischemia-reperfusion or statin experiment .INa was recorded by whole-cell patch clamp, and I/Imax （ normalized I Na at -40 mV ） , V1/2 and k were calculated and compared among 3 groups.Results （1） Normal basic levels were no difference among 3 groups.Basic ischemia level of 3 groups：after ischemia for 20 min, compared with normal state , normalized I Na , V1/2 and k decreased （ t=2.861, 9.462, 6.264, all P〈0.01）, and there were no differences among the 3 groups.（2） Compared with ischemia for 20 min, ischemia-reperfusion group I Na of reperfusion for 3 min were decreased from＆amp;nbsp;0.83 ±0.11 vs 0.57 ±0.09 （P〈0.01）.In statin group INa were decreased from 0.92 ±0.04 vs 0.72 ± 0.05（P〈0.01）, but there were no change in control group .Compared with control group , the currents of ischemia-reperfusion and statin group were decreased , while statin group were increased compared with ischemia-reperfusion group （F =23.738, P〈0.05）.（3） Activation parameters in reperfusion phase：compared with ischemia baseline, at the first 3 min of reperfusion, V1/2 and k in control group were not changed, while they both increased in ischemia-reperfusion group （V1/2： -58.87 ±3.36 mV vs -54.33 ± 2.40 mV, k 1.25 ±0.59 vs

关 键 词：阿托伐他汀 钠电流 缺血再灌注 

分 类 号：R96[医药卫生—药理学]