西洛他唑对大鼠右心室肌细胞离子通道的影响

Effect of Cilostazol on the Ion Channel of Right Ventricular Cells in Experimental Rats

目的：观察西洛他唑对大鼠右心室肌细胞离子通道的影响，探讨西洛他唑预防Brugada综合征室性心律失常发生的离子通道机制。 方法：本研究包括两部分实验：①灌流实验，分为1、2、5、50μmol/L西洛他唑组，每组记录的细胞数分别为9、5、3、7个。分别观察每组给药前后瞬间外向钾电流（Ito）电流密度的变化，并观察四组间用药前后Ito电流密度变化的差异；②口服药物实验，分为空白1组、实验1组、空白2组、实验2组，每组选用的大鼠数分别为7、5、8、6只，分别观察实验组与空白组Ito、L-型钙电流（ICa,L）电流密度的差异。 结果：灌流实验结果：①在1、2、5、50μmol/L西洛他唑各组中，细胞灌流药物后Ito电流密度均降低，在自指令电压＋60 mV时，各组用药前后的Ito电流密度差异有统计学意义（P均＜0.05）。②在各指令电压下时，不同浓度西洛他唑灌流液灌流细胞后Ito电流密度减少率，四组间差异均无统计学意义（P均〉0.05）。口服药物实验结果：①在自指令电压-50 mV到最大＋60 mV，实验1组Ito电流密度较空白1组无明显变化，差异无统计学意义（P〉0.05）；②在自指令电压为＋10 mV，空白2组ICa,L电流密度较实验2组略高，但差异无统计学意义（P〉0.05）。 结论：1、2、5、50μmol/L西洛他唑灌流液直接作用于大鼠右心室肌细胞，均能明显的抑制Ito，但西洛他唑1~50μmol/L范围内对Ito的抑制程度没有差异。西洛他唑可能具有抑制Brugada综合征心律失常发生的作用。

Objective： To observe the effect of cilostazol on the ion channel of right ventricular cells in experimental rats, and to explore the ion channel mechanism of ciolstazol for preventing the ventricular arrhythmia in Brugada syndrome. Methods： Our research was composed of 2 groups： ①Perfusion group, the cells were treated in 4 sub-groups by cilostazole at 1, 2, 5, 50μmol/L respectively, and there were 9, 5, 3, 7 cells were recorded at each sub-group to observe the differences of current density Ito at before and after treatment. ②Oral group, which included 4 sub-groups：Control 1 with 7 rats, Experiment 1 with 5 rats, and Control 2 with 8 rats, Experiment 2 with 6 rats respectively. The differences of current density Ito and ICa,L were studied between each Control and Experiment sub-groups. Results： In Perfusion group,①with cilostazole 1, 2, 5, 50μmol/L treatment, the current density Ito decreased in all sub-groups, when the self-command voltage at＋60mV, the Ito was signiifcantly different in each sub-group at before and after treatment, all P〈0.05.②When each command voltage decreasing, the reduction rates of Ito were similar among 4 sub-groups, all P〉0.05. In Oral group,①When the self-command voltage from-50mV reached the maximum of＋60mV, the Ito was similar between Control 1 and Experiment 1 sub-groups, P〉0.05.②When the self-command voltage at＋10mV, the current density of ICa,L was slightly higher in Control 2 sub-group than that in Experiment 2 sub-group, P〉0.05. Conclusion： Direct perfusion of cilostazole in right ventricular cells may inhibit Ito in experimental rats, such effect was similar with cilostazole treatment at （1-50）μmol/L. Cilostazole might prevent the ventricular arrhythmia in Brugada syndrome in experimental rats.