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目的研究甲基苯丙胺对心血管系统的毒性作用及其机制。方法分离豚鼠心室肌细胞,采用全细胞膜片钳技术获取并分析心室肌细胞延迟整流钾电流(IK)及动作电位(AP)水平。结果甲基苯丙胺0.5mmol·L-1使豚鼠心室肌细胞AP幅值从121.6mV降至106.0mV,能延长动作电位时程(APD),但不改变静息电位水平。其中动作电位复极10%,25%,50%,75%及90%时程(APD10,APD25,APD50,APD75,APD90)分别延长179.0%,88.7%,47.7%,43.4%和31.9%(P<0.05)。甲基苯丙胺0.5mmol·L-1使快速激活延迟整流钾电流(IKr)和缓慢激活延迟整流钾电流(IKs)的膜电位水平降低,电流-电压曲线下移,但曲线形状不变,冲洗后能部分恢复。用含甲基苯丙胺0.01,0.1,0.5,1.0和3.0mmol·L-1的细胞外液分别灌流细胞5min,甲基苯丙胺对IKr尾电流幅度呈浓度依赖性的阻断作用,冲洗后能部分恢复。甲基苯丙胺对IKs尾电流的影响也非常显著(P<0.05)。结论甲基苯丙胺对豚鼠心室肌细胞的IK及AP都有不同程度的影响,这可能是甲基苯丙胺造成心脏损伤的电生理机制之一。
Objective To study the toxic effects of methamphetamine on cardiovascular system and its mechanism. Methods The guinea pig ventricular myocytes were isolated and the delayed rectifier potassium current (IK) and action potential (AP) were measured by whole cell patch clamp technique. Results 0.5 mmol·L -1 methamphetamine decreased the AP amplitude of guinea pig ventricular myocytes from 121.6 mV to 106.0 mV, prolonging the APD but not changing the resting potential. The duration of APD10, APD25, APD50, APD75 and APD90 were prolonged by 179.0%, 88.7%, 47.7%, 43.4% and 31.9%, respectively, at 10%, 25%, 50%, 75% and 90% <0.05). Methamphetamine 0.5mmol·L-1 decreased the membrane potential of IKr and IKs, and the current-voltage curve decreased but the shape of the curve remained unchanged. After washing Can be partially restored. The cells were perfused with 0.01%, 0.1%, 0.5%, 1.0% and 3.0mmol·L-1 extracellular fluids containing methamphetamine for 5min. Methamphetamine blocked the IKr tail current concentration in a concentration-dependent manner and partially recovered after washing . The effect of methamphetamine on IKs tail currents was also significant (P <0.05). Conclusions Methamphetamine has different effects on IK and AP in guinea pig ventricular myocytes, which may be one of the electrophysiological mechanisms of methamphetamine causing heart damage.