碘化N-正丁基氟哌啶醇对大鼠心肌细胞内钙离子的影响  

Effects of N-n-butyl haloperidol iodide on intracellular calcium in rat cardiomyocytes

作　　者：黄展勤[1] 石刚刚[1] 高分飞[1] 周燕琼[1] 张艳美[1] 刘幸平[1] 

机构地区：[1]汕头大学医学院药物研究室

出　　处：《中国临床药理学与治疗学》2006年第5期485-490,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(№30070304);国家新药研究基金(№9690105231);广东省自然科学基金重点项目(№621235)

摘　　要：目的:研究碘化N-正丁基氟哌啶醇(F2)对大鼠心肌细胞内钙离子([Ca2+]i)的影响。方法:采用钙荧光染料Fluo-3-AM负载心肌细胞,在激光扫描共聚焦显微镜上测定细胞内钙离子的变化。结果:在含钙(1.8mmol·L-1)台式液中,60mmol·L-1KCl使细胞内钙荧光强度由1.0增高至1.84±0.35(P<0.01,n=50),分别用0.1、1、10μmol·L-1F2预先孵育心肌细胞,F2可以浓度依赖地抑制钙荧光强度的增高,IC50为1.61μmol·L-1。0.1、1、10μmol·L-1F2使得KCl诱导增高的钙荧光强度从1.92±0.42分别降至1.88±0.39、1.31±0.36和1.09±0.05(P分别>0.05、<0.01和<0.01,n=50),IC50为1.78μmol·L-1。F2不影响静息状态下的细胞内钙的浓度。对咖啡因和三磷酸肌醇介导的细胞内钙的释放均无作用。结论:F2通过阻断心肌细胞膜电压依赖性钙通道降低心肌细胞内钙浓度,这可能是保护心肌缺血/再灌注损伤的机制。AIM： To investigate the effects of N-n- benzyl haloperidol iodide （ F2 ） on intraeelltdar calcium （ [ Ca^2 ＋ ]i ） in rat cardiomyocytes. METHODS： Cardiomyocytes were loaded with Fluo3-AM, a calcium sensitive fluorescent dye, and the [ Ca^2＋ ]i was determined by the use of laser scanning confocal microscope （LSCM）. RESULTS： In the Tyrode＇s solution with Ca^2＋ at the concentration of 1.8 mmol· L^- 1, 60 mmol· L^- 1 KCl induced a rapid increase of intracellular calcium fluorescence intensity （FI）. The FI was increased from the basic value （1.0） to 1.84±0.35 （P〈0.01,n =50）. With preincubation of cardiomyocytes with F2 0.1, 1, 10 μmol· L^-1, the FI elevation was inhibited in a concentration-dependent manner. The calculated IC50 was 1.61 μmol·L^-1.F2 also reduced the FI elevated by 60mmol· L^- 1 KCl in a concentration dependent manner. The FI was decreased by 0.1,1,10 μmol· L^-1 F2 from 1.92±0.42（n = 50）to 1.88 ± 0.39（P 〉 0.05, n = 50）, 1.31±0.36（P 〈 0.01, n = 50）, 1.09 ± 0.05（P 〈 0.01, n= 50）, respectively. The calculated IC50 was 1.78μmol· L^-1. F2 had no effects of on[Ca^2 ＋ ]i in the resting state, and had no effects on intracellular calcium release induced by caffeine and inositol-1, 4, 5-trisphosphate.CONCLUSION： F2 reduces[Ca^2＋ ]i. via inhibition of voltage dependent calcium channel, which is possibly involved in the mechanism of its protective effects on myocardial ischemia/reperfusion injury.

关 键 词：氟哌啶醇 心肌细胞 钙 激光扫描共聚焦显微镜 

分 类 号：R965.2[医药卫生—药理学]