阿托伐他汀对大鼠左室心肌细胞瞬时钠通道电流的作用

目的观察阿托伐他汀对正常和模拟缺血大鼠左室心肌细胞瞬时钠通道电流(INa)的作用。方法Wist-ar大鼠30只,用于分离左室心肌细胞。细胞按异体配对原则分为他汀组(阿托伐他汀5μmol/l+乙醇8.575mmol/L)和对照组(乙醇8.575 mmol/L)。采用全细胞膜片钳技术记录INa:测定正常和模拟缺血状态下,用药前和用药后3～5 min的数据;比较标准化INa峰值、半激活电压(V1/2)、激活曲线斜率(k)和衰减时间常数(τ)。结果正常状态下,他汀组用药后在-40 mV、-35 mV和-30 mV测试电位下的标准化INa峰值分别由0.93±0.14,0.92±0.06和0.88±0.08降低至0.68±0.16,0.68±0.17和0.65±0.18(P均<0.01);用药前后V1/2、k不变;用药后在-30 mV、-25 mV和-20 mV测试电位下的τ值(ms)分别由1.22±0.27,1.12±0.23和1.04±0.21延长至1.34±0.33,1.24±0.31和1.17±0.30(P均<0.05)。他汀组用药后对模拟缺血细胞INa的作用和正常细胞的作用相似。对照组对照液使用后不引起INa上述指标的变化。结论阿托伐他汀对正常和模拟缺血状态的大鼠左室心肌细胞的INa均有钠通道阻滞样作用。

The effects of atorvastatin on INa of the rat left ventricular cells

Objective To observe the effects of atorvastatin on transient sodium currents （INa） of the normal and simulated ischemic cells in rat left ventricle. Methods Thirty Wistar rats, which were used for isolating left ventricular cells, were randomly divided into two groups： statin group （5 μmol/L atorvastatin ＋ 8. 575 mmol/L alcohol） and control group （8. 575mmol/L alcohol）. INa was recorded before and after administration for 3 -5min by whole-cell patchclamp, respectively in the normal and simulated ischemic state, comparing the normalized peak currents, membrane potential at 50% maximal activation （ V1/2 ）, offsetting of activation curve （k） and decay constant （τ）. Results In statin group of the normal state, after administration the normalized currents were decreased （0.93 ± 0.14 vs 0.68 ±0.16, 0.92 ±0.06 vs 0.68± 0.17 and 0.88 ± 0.08 vs 0.65 ± 0.18, separately at the testing potential of - 40 mV, - 35 mV and - 30 mV, P〈0.01）, while the τ values （ms） were increased （1.22 ± 0.27 vs 1.34 ±0.33, 1.12 ± 0.23 vs 1.24 ± 0. 31 and 1.04 ± 0.21 vs 1.17 ± 0.30, separately at -30 mV, -25 mV and -20 mV, P〈0.05）, but V1/2 and k were not changed. After administration, all indexes in the statin group of simulated ischemic state were similar to that the normal state. In control group, the indexes of INa were not changed. Conclusions Atorvastatin plays a role like sodium channel block in rat left ventricular cells both at the state of normal and simulated ischemia. [ Chinese Journal of Cardiac Pacing and Electrophysiology ,2009,23 （ 5 ） ：420 -423 ]