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目的:探讨姜黄素对人Kv1.3通道的药理作用。方法:通过建立稳定表达在HEK-293细胞上的人Kv1.3通道细胞系,运用全细胞膜片钳技术研究姜黄素对Kv1.3通道的作用,并通过在体动物实验观察药物对兔体表心电图的影响(心率和QTc间期),初步验证药物对心脏的安全性。结果:姜黄素可以时间依赖性和浓度依赖性地阻断Kv1.3通道,半数抑制浓度IC50为4.21μmol/L,而且通道激活曲线向右移动(正电压方向),说明药物对通道的激活状态(开放)产生阻断作用。动物实验发现,在较低浓度时(5或10μmol/L)姜黄素对兔心率和QTc间期没有产生任何影响,在高浓度时(50μmol/L)只是轻微地降低心率和延长QTc间期,无严重心律失常发生。结论:姜黄素可以有效阻断人Kv1.3通道,并且在一定范围内无致心律失常作用,具有相对安全性。本研究为姜黄素治疗自身免疫性疾病的药理机制提供了更多理论基础。
Objective: To explore the pharmacological effects of curcumin on human Kv1.3 channel. Methods: The effect of curcumin on Kv1.3 channel was studied by whole cell patch clamp technique by establishing a human Kv1.3 channel cell line stably expressed on HEK-293 cells. The effect of curcumin on Kv1.3 channel was also studied. ECG effects (heart rate and QTc interval), preliminary verification of drug-to-heart safety. Results: Curcumin blocked Kv1.3 channels in a time-dependent and concentration-dependent manner with IC50 of 4.21μmol / L, and the activation curve of the channel shifted to the right (positive voltage direction), indicating that the activation state of the channel (Open) have a blocking effect. Animal experiments showed that curcumin had no effect on rabbit heart rate and QTc interval at low concentrations (5 or 10 μmol / L), and slightly decreased heart rate and prolonged QTc interval at high concentrations (50 μmol / L) No serious arrhythmia occurs. CONCLUSION: Curcumin can effectively block human Kv1.3 channel and has no relative arrhythmia effect in a certain range. This study provides more theoretical basis for the pharmacological mechanism of curcumin in the treatment of autoimmune diseases.