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目的:研究小檗碱衍生物CPU86017对抗房颤作用及其离子通道机制。方法:运用膜片钳技术在稳定表达人心房肌Kv1.5钾通道细胞系(HEK293)及豚鼠心房肌细胞上观察CPU86017对超速整流钾通道(IKur)的作用,观察CPU86017(1.25或2.5mg·kg-1)对比阳性药azimilide(3mg·kg-1)对乙酰胆碱(ACh)和CaCl2诱发的大鼠房颤的治疗作用。结果:CPU86017依浓度抑制IKur,对豚鼠心房肌细胞和培养的HEK293细胞上IKur的半数抑制浓度(IC50)分别是4.56和0.21μmol·L-1。在乙酰胆碱(ACh)和CaCl2诱发的房颤模型上,CPU86017有效缩短房颤持续时间,逆转房颤所致心房有效不应期(AERP)的缩短。结论:CPU86017能抑制KV1.5编码的电流IKur,改善房颤大鼠心房ERP的病变,有效对抗房颤。
Objective: To study the effects of berberine derivative CPU86017 on atrial fibrillation and its ion channel mechanism. Methods: The effects of CPU86017 on IKUR were observed by patch-clamp technique in Kv1.5 cell line stably expressing human atrial myocardium (HEK293) and in guinea pig atrial myocytes. The effects of CPU86017 (1.25 or 2.5 mg · kg-1) compared with the therapeutic effect of azimilide (3 mg · kg -1) on acetylcholine (ACh) and CaCl 2 -induced atrial fibrillation in rats. Results: The concentration of IKur inhibited the concentration of IKur, and the IC50 of IKur on guinea pig atrial myocytes and HEK293 cells were 4.56 and 0.21μmol·L-1, respectively. In acetylcholine (ACh) and CaCl2-induced atrial fibrillation models, CPU86017 effectively shortens the duration of atrial fibrillation and reverses the shortening of atrial fibrillation-induced atrial refractory period (AERP). Conclusion: CPU86017 can inhibit the current IKur encoded by KV1.5, improve the atrial ERP in atrial fibrillation rats and effectively prevent atrial fibrillation.