小檗碱衍生物CPU 86017抑制KV1.5电流（IKur）及对抗SD大鼠房颤作用

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。

Effects of Berberine Derivate CPU 86017 on I_(Kur) Currents and Experimental Atrial Fibrillation

AIM：Compared with azimilide,the present study was designed to observe the anti-atrial fibrillation（AF） effects of CPU 86017,a berberine derivative,and explore its possible ion-channel mechanism.METHODS：The effects of CPU 86017 on ultra-rapid delayed rectifier K＋ current（IKur） was studied both on guinea pigs atrial cardiomyocytes and human embryonic kidney（HEK） 293 cell line with whole-cell patch clamp technique.Anti-AF action of CPU 86017（1.25,2.5 mg·kg^-1,ip） was observed in AF model rats induced by acetylcholine（ACh）-CaCl2.RESULTS：CPU 86017 inhibited IKur in a concentration-dependent manner.The IC50 of IKur on atrial myocytes and HEK293 cells was 4.56 and 0.21 μmol·L^-1,respectively.On the AF rats,CPU 86017 effectively shortened AF duration,prolonging atrial effective refractory period（AERP） by 38.9% in rats atrial.CONCLUSION：CPU86017 inhibited IKur in a concentration-dependent manner.It was effective in treating AF partly by inhibiting IKur and prolonging AERP.