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目的 研究腹主动脉结扎诱发大鼠肥厚心肌L-型钙电流的变化以及用氯沙坦治疗对此变化的影响。方法 用结扎腹主动脉的方法诱发大鼠心肌肥厚模型。用全细胞膜片钳技术记录肥厚左心室肌细胞L-型钙电流。结果 肥厚组心肌细胞膜电容 (148±29 pF) 明显大于假手术组 (102±14 pF, P<0.01) 和氯沙坦治疗组 (118±27, P<0.01)。肥厚组ICa,L 峰值及电流密度均大于假手术组 (-835±124 pA vs -1404±417 pA 和(7.5±1.8 pA·pF-1 vs -0.5±2.2 pA·pF-1, P<0.01)。氯沙坦治疗组ICa,L 峰值 (-956±170 pF) 及电流密度 (-8.2±1.6 pA·pF-1) 均比肥厚组明显减小 (P<0.05)。肥厚组半数激活电压 (-20.6±1.0 mV)与假手术组 (-15.6±1.6 mV) 及氯沙坦治疗组 (-17.4±1.0 mV) 相比向负向移动 (P<0.01)。肥厚组激活曲线斜率 (5.7±0.4)比假手术组 (6.4±0.5) 略减小 (P<0.05)。肥厚组半数失活电压 (-27.6±1.9 mV) 比假手术组 (-31.4±2.2 mV) 略正移 (P<0.05)。三组心肌失活曲线斜率无差异。结论 氯沙坦 (30 mg·kg-1·d-1, ig) 可防止腹主动脉结扎诱发大鼠心肌细胞肥大的发生及相关的L-型钙电流的变化。
Objective To study the changes of L-type calcium current in hypertrophic myocardium induced by ligation of abdominal aorta and the effect of losartan on the changes. Methods The rat model of cardiac hypertrophy was induced by ligating the abdominal aorta. Whole-cell patch-clamp technique was used to record L-type calcium current in hypertrophic left ventricular myocytes. Results The membrane capacitance (148 ± 29 pF) in hypertrophic group was significantly higher than that in sham operation group (102 ± 14 pF, P <0.01) and losartan treatment group (118 ± 27, P <0.01). The ICa, L peak and current density in hypertrophic group were significantly higher than those in sham operation group (-835 ± 124 pA vs -1404 ± 417 pA and (7.5 ± 1.8 pA · pF-1 vs -0.5 ± 2.2 pA · pF-1, P <0.01 ), The peak of ICa, L (-956 ± 170 pF) and the current density (-8.2 ± 1.6 pA · pF-1) in losartan group were significantly lower than those in hypertrophic group (P <0.05) (-20.6 ± 1.0 mV) compared with sham operation group (-15.6 ± 1.6 mV) and losartan treatment group (-17.4 ± 1.0 mV) (P <0.01) .The activation curve slope of hypertrophy group (5.7 ± 0.4) was slightly lower than that of the sham operation group (6.4 ± 0.5) (P <0.05), and the half inactivation voltage (-27.6 ± 1.9 mV) in the hypertrophic group was slightly positive than that in the sham operation group (-31.4 ± 2.2 mV) <0.05) .Conclusion Losartan (30 mg · kg-1 · d-1, ig) can prevent the occurrence of cardiomyocyte hypertrophy induced by abdominal aorta ligation and the related L - type of calcium current changes.