缺血再灌注期间不同时相氟比洛芬酯处理对乳鼠心肌细胞钠电流的影响

目的：研究缺血再灌注（ischemia/reperfusion，I/R）期间不同时相（缺血时、缺血后再灌时）氟比洛芬酯处殚对乳鼠心肌细胞钠电流的影响。方法：实验分为四组：1组（对照组）为体外培养乳鼠心室肌细胞；Ⅱ组（I/R组）为相同的细胞，缺血3小时，再灌注1小时；III组（氟比洛芬酯缺血时处理组）在I/R缺血时相加入氟比洛芬哺（0.15μM）；IV组（氟比洛芬酯缺血后再灌注时处理组）在I/R再灌注时相加入氟比洛芬酯（0．15μM）。采用膜片钳全细胞模式分别记录并比较四组的钠电流。结果：和I组相比，II组存每一指令电压上都增大钠电流；在测试电压为-20mV的条件下，钠电流峰值电流密度从-375．47±70．31（pA/pF）增至-557．11±12786（pA/pF）（n=5，P〈f0.05）；稳态激活半激活电压（V1/2）分别为-4281±1．21mV和-3149±2．40mV（n=5，P〈005）；稳态欠活半激活电压（V1/2）分别为-7424±5．89mV和-68．70±6．26mV（n=5，P〈005）；通道失活后恢复T分别为2569±19．47ms和7．534±3．24ms（n=5，P〈0．05）。III、IV组钠电流峰值电流密度从-375．47±70．31（pA/pF）分别降至-208．80±121．44和-278．91±188．26（pA/pF）（n=5，P〈0．05）；通道稳念激活V1/2分别为-40．89±9．81mV和-39．49±3．70mV（n=5，P〉O05）；稳态失活V1/2分别为74．45±5．02mY和-75494±3．32mV（n=5，P〉0．05）；通道失活后恢复T分别为24．98±16．41ms和26．30±11．82ms（n=5，P〉005）。III、IV组之间各指标间的差异无统计学意义。结论：I/R处土型可以增大钠电流的峰值电流，并使电压电流曲线下移；减慢通道的时间依赖性激活，促进通道的电爪依赖性失活，失活后恢复变快。而在I/R缺血和再灌注两个时相使用氟比洛芬酯均能有效阻制钠通道的这螳改变。

Effects of Flurbiprofen Axetil Management on the Sodium Current of the Cardiomyocytes from the New-Born Rats at Different Stages of lschemia/Reperfusion

Objective To study the effects offlurbiprofen axetil （FA） management on the sodium current of the cardiomyocytes from the ventricles of the new-born rats at different stages of ischemia/reperfusion （l/R）. Method the cells were classified into four groups： group I （the control group）： the normal cardiomyocytes from new-born rats; group 11 （the I/R group）： the same cardiomyocytes that were treated under the condition of ischemia for three hours and repcrfusion for one hour; group III： the same cardiomyocytes that were treated with FA （0.15μM） during ischemia stage of I/ R; group IV： the same cardiomyocytes that were treated with FA （0.15μM） during reperfusion stage of I/R. The sodium currents from the above four groups were recorded and compared by whole cell patch clamp technique. Result compared with the control group, the sodium currents of all the cardiomyocytes frome the I/R group at all the test potentials increased; at the test potential of -20 mV, the peak sodium current increased from -375.47±70.31 （pA/pF） to -557.11±127.86 （n-5, P〈0.05）; the half-maximal voltage （VI/2） of the steady-state activation were -42.81±1.21mV and -31.49±2.40mV （n=5, P〈0.05）; V1/2 of the steady-state inactivation were -74.24±5.89mV and -68.70±6.26mV （n=5, P〈0.05） ; channel recovery time constant were 25.69±19.47ms and7.53±3.24ms （n=5, P〈0.05）; as for group III and IV, the peak sodium current decreased from -375.47±70.31（pA/ pF） to -208.80±121.44 and -278.91±188.26 （pA/pF） （n 5, P〈0.05）; V1/2 of of the steady-state activation were -40.89±9.81mV and -39.49±3.70mV （n-5, P〉 0.05）; V1/2 of of the steady-state inactivation were -74.45±5.02mV and-75.49±3.32mV （n 5, P〉 0.05） ; channel recovery time constant were 24.98±16.41ms and 26.30±11.82ms （n-5, P〉 0.05）. The differences between the parameters from group 111 and IV had no statistical significance. Conclusion I/R treatment could increased the peak sodium current and down-shifted the voltage-current curve; slowed the time-dependent activation of the sodium channel and promoted inactivation of voltage-dependent of the sodium channel; recovered faster after the I/R management. FA management at both ischemia and reperfusion stage of I/R might inhibit changes of sodium current caused by I/R treatment.