心室快钠电流在不同模拟缺血时间的变化及阿托伐他汀的作用

The change of ventricular INa at different time of simulated ischemia and the effect of atorvastatin

目的观察不同模拟缺血时间下大鼠左室心肌细胞快钠电流（INa）的变化规律和阿托伐他汀对该过程的影响。方法Wistar大鼠共30只，分离左室心肌细胞，分为缺血组（正常→模拟缺血）和他汀组（正常→模拟缺血＋5μmol／L阿托伐他汀）。用全细胞膜片钳记录两组正常状态INa（对照），再从模拟缺血3～21min，每2min记录1次，检测标准化INa峰值；比较正常和模拟缺血3min时INa的门控参数。结果①标准化INa峰值（测试电位-40mV）：缺血组正常状态下为0．95±0．04，与正常状态比，缺血3min时增至1．15±0．08（P〈0．01）并达峰，9min和11min时分别降至0．98±0．12和0．92±0．12（均P〉0．05），至21min时减至0．56-t-O．13（P〈0．01）；他汀组在缺血3min时和正常状态比无差别（分别为0．92±0．12和0．97±0．04，P〉0．05）。②门控参数：由正常状态至缺血3min状态，缺血组半激活电压（U1/2,a）、激活曲线斜率（Ka）、半失活电压（K1/2,i）和恢复时间常数（τ）均减小（均P〈0．01），失活曲线斜率（Ki）不变；组间比较，他汀组K值下降（P〈0．05），τ值减小程度弱于缺血组（P〈0．05）。结论模拟缺血对INa变化的作用呈时间依赖性；阿托伐他汀可通过改变门控特性来抑制这一达峰过程。

Objective To observe time dependent effects of simulated ischemia on transient sodium currents （INa） of rat left ventricular myocytes, and the effect of atorvastatin on ischemia INa. Methods Thirty Wistar rats were used for isolating left ventricular myocytes, which were randomly divided into two groups ： ischemia group （ normal → simulated ischemia） and statin group （normal → simulated ischemia with 5 μ mol/L atorvastatin）. INa were recorded in normal condition （for control） by whole-cell patchclamp. Then in simulated ischemia condition, INa were recorded from 3 to 21 min, normalized peak currents were monitored every 2 min, and gate parameters were compared between normal and simulated isehemia （3 min） condition. Results ①Normalized peak currents （at -40 mV ） ： in ischemia group, compared with normal （0.95 ±0.04）, the currents in simulated isehemia were increased to peak at 3 rain （ 1.15 ±0.08, P 〈0.01 ）, decreased at 9 min and 11 rain （0.98 ± 0.12 and 0.92 ± 0.12, P 〉 0.05, respectively） , and half attenuated at 21 min （0. 56 ±0.13, P 〈0.01 ） ; in statin group, there were no differences between nomal and simulated isehemia condition at 3 min （0.97 ±0.04 vs 0.92 ± 0. 12, P 〉 0.05 ）. ②Gate parameters： from normal to simulated ischemia condition at 3 min, membrane potential at 50% maximal activation （ V1/2,a ） , offsetting of activation curve （ Ka ）, membrane potential at 50% maximal inactivation （V1/2,i） and deinactivation constant （τ） were decreased （P 〈 0.01, respectively） in ischemia group, but offsetting of inactivation curve （ Ka ） were not changed ; Compared between two groups, Ka of statin group were decreased （ P 〈 0.05 ） and the decrease of τ value in statin group were less than that in ischemia group （ P 〈 0.05 ）. Conclusions The effects of simulated ischemia on INa are time dependent, and atorvastatin can depress this process.