小檗碱衍生物CPU 86017抑制K_V1.5电流(I_(Kur))及对抗SD大鼠房颤作用(英文)  

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

作　　者：汤依群[1] 郭香[1] 陈春林[1] 尹月淼[1] 汪旻晖[1] 孙书娟[1] 戴德哉[1] 

机构地区：[1]中国药科大学临床药学教研室,南京210009

出　　处：《中国天然药物》2010年第3期212-217,共6页

基　　金：supported by National Natural Science Foundation of China(No.30230170)~~

摘　　要：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。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.

关 键 词：抗心律失常药 房颤 CPU86017 离子通道 超速延迟整流钾通道 

分 类 号：R965[医药卫生—药理学]