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雷诺嗪对家兔舒张性心力衰竭心室肌细胞晚钠电流的影响

Effect of ranolazine on late sodium current in rabbits with diastolic heart failure
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摘要 目的探讨雷诺嗪对家兔舒张性心力衰竭动物模型心室肌细胞晚钠电流的影响。方法健康家兔24只,随机分为假手术组、模型组、河豚毒素(tetradotoxin,TTX)组和雷诺嗪组,每组6只。4组均采用腹主动脉缩窄法制备兔左心室压力超负荷模型,其中假手术组仅游离腹主动脉而不行缩窄术。模型制作8周后取各组兔心室肌细胞进行试验,记录电流前3min,TTX组灌流2μmol/L TTX,雷诺嗪组灌流10μmol/L雷诺嗪,假手术组和模型组均灌流无钙和钾的细胞外液,应用全细胞膜片钳技术记录1、3、5 Hz刺激频率下各组兔心室肌细胞晚钠电流成分,并进行比较。结果 1、3、5 Hz刺激频率下,模型组晚钠电流成分[(5.45±0.49)、(5.33±0.46)、(5.51±0.50)pA/pF]明显高于假手术组[0、0、0pA/pF]、TTX组[(3.88±1.05)、(3.78±0.12)、(3.81±1.06)pA/pF]和雷诺嗪组[(4.80±0.33)、(4.76±0.38)、(4.35±0.39)pA/pF](P<0.05),TTX组和雷诺嗪组高于假手术组(P<0.05),TTX组与雷诺嗪组比较差异无统计学意义(P>0.05);模型组和TTX组在1、3、5Hz刺激频率下的晚钠电流成分比较差异无统计学意义(P>0.05),雷诺嗪组在5Hz刺激频率下的晚钠电流成分低于3Hz和1Hz时,3Hz时低于1 Hz时(P<0.05)。结论雷诺嗪可抑制超负荷家兔心室肌细胞晚钠电流,改善舒张性心力衰竭的功能。 Objective To investigate the effect of ranolazine on late sodium current of heart ventricular myocytes in rabbit models with diastolic heart failure.Methods Twenty-four healthy rabbits were randomly divided into sham operation group,model group,tetradotoxin(TTX)group and ranolazine group,with 6 rabbits in each group.The left ventricular pressure overload model was prepared by abdominal aortic constriction in 4 groups,in which sham operation group was performed only free abdominal aorta without coarctation.After 8 weeks,the ventricular myocytes were obtained.TTX group was perfused with 2μmol/L of TTX,ranolazine group was perfused with 10μmol/L of ranolazine,and sham operation group and model group were perfused with calcium-free and potassium-free extracellular fluid 3 min before the current was recorded.The late sodium current components of ventricular myocytes in rabbits at 1,3 and 5 Hz stimulation frequencies were recorded by whole cell patch clamp technique and compared.Results At 1,3 and 5 Hz stimulation frequencies,the compositions of late sodium current in model group((5.45±0.49),(5.33±0.46),(5.51±0.50)pA/pF)were significantly higher than those in sham operation group(00,0 pA/pF),TTX group((3.88±1.05),(3.78±0.12),(3.81±1.06)pA/pF)and ranolazine group((4.80±0.33),(4.76±0.38),(4.35±0.39)pA/pF)(P<0.05),and in TTX group and ranolazine group than those in sham operation group(P<0.05),and there were no significant differences between TTX group and ranolazine group(P>0.05).The late sodium current components showed no significant differences at 1,3 and 5 Hz stimulation frequencies in both model group and TTX group(P>0.05).The late sodium current frequency at 5 Hz stimulation was significantly lower than that at 3 and 1 Hz,and in 3 Hz than at 1 Hz in ranolazine group(P<0.05).Conclusion Ranolazine could inhibit the late sodium current of ventricular myocytes in rabbits with overload pressure and improve the function in rabbits with diastolic heart failure.
出处 《中华实用诊断与治疗杂志》 2017年第12期1171-1174,共4页 Journal of Chinese Practical Diagnosis and Therapy
基金 黑龙江省科技厅项目(QC2011C090)
关键词 舒张性心力衰竭 盐酸雷诺嗪 晚钠电流 膜片钳 Diastolic heart failure ranolazine late sodium current patch clamp techniques rabbits
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