培哚普利对心力衰竭大鼠心肌细胞钙瞬变及其调控蛋白的影响  

Effects of ACE inhibitor on the calcium transient and calcium handling proteins in ventricular myocytes from rats with heart failure

作　　者：王礼春[1] 马虹[1] 何建桂[1] 廖新学[1] 麦炜颐[1] 陈文芳[2] 冷秀玉[1] 马莉[1] 曾武涛[1] 柳俊[1] 陶军[1] 董吁钢[1] 唐安丽[1] 冯冲[1] 

机构地区：[1]中山大学附属第一医院心血管内科,广州510080 [2]中山大学附属第一医院肾病实验室,广州510080

出　　处：《中华心血管病杂志》2005年第6期513-517,共5页Chinese Journal of Cardiology

摘　　要：目的研究培哚普利在心力衰竭(心衰)治疗中对心肌细胞的收缩特性、钙瞬变及其调控蛋白的影响。方法通过缩窄雄性Wistar大鼠的腹主动脉,制成压力负荷增高性心衰模型。随机分成培哚普利治疗组(培哚普利组,3mg·kg-1·d-1)、心衰对照组和假手术对照组(假手术组)。12周后分离左室心肌细胞,测定单个心肌细胞在电刺激时的缩短分数、钙瞬变以及钠-钙交换蛋白(NCX1)、内质网Ca2+-ATPase(SERCA2)、受磷蛋白等钙调控蛋白的转录与翻译水平。结果心肌细胞的缩短分数(FS)和[Ca2+]imax在心衰对照组均明显低于假手术组[FS(%):7.51±1.15与13.21±1.49,[Ca2+]imax(nmol/L):330.85±50.05与498.16±14.07;均为P<0.01]。给予培哚普利治疗后,培哚普利组的FS和[Ca2+]imax分别为(10.89±1.18)%和(488.72±22.27)nmol/L,明显高于心衰对照组(均为P<0.01)。在心衰对照组,NCX1和受磷蛋白的mRNA水平显著高于假手术组,而SERCA2的mRNA却明显低于假手术组。在培哚普利组,其NCX1和SERCA2的mRNA水平则介于心衰对照组和假手术组之间,差异有统计学意义(均为P<0.05)。在心衰对照组及培哚普利组,NCX1的蛋白表达量分别是假手术组的(1.141±0.047)倍(P<0.01)和(1.074±0.081)倍(P=0.018),SERCA2的表达量则是假手术组的(0.803±0.100)倍(P<0.01)和(0.893±0.084)倍(P=0.003)。结论培哚普利抗心衰治疗能够减轻心肌细胞的钙瞬变及其调控蛋白的异常变化,使心衰中单个心肌细胞的收缩特性得到保护。Objective To investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transient and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.Methods Male Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg·kg -1 ·d -1 ), heart failure group without treatment (CHF-C) and sham-operated group(PS) after heart failure was induced by constricting abdominal aorta for 16 weeks. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated, and single cell shortening fraction and [Ca 2+ ]_i were simultaneously measured through laser scanning confocal microscope under the field stimulation (1.0 Hz). RT-PCR and Western blot were performed to evaluate the level of mRNA and protein of Na +-Ca 2+ exchanger (NCX_1), sarcoplasmic Ca 2+ -ATPase (SERCA_2) and phospholamban (PLB).Results The fraction of cell shortening (FS %) and [Ca 2+ ]_ i max (nmol/L) were significantly smaller in group CHF-C than group PS (FS%:7.51±1.15 vs 13.21±1.49;[Ca 2+ ]_ i max :330.85±50.05 vs 498.16±14.07; both P <0.01). And in CHF-T group, FS and [Ca 2+ ]_ i max were greater than those in CHF-C group. In CHF-C group, the left ventricular mRNA of NCX_1 and PLB were significantly higher than those in PS group (R_ NCX_1/β-Actin :0.51±0.12 vs 0.19±0.06, P <0.01;R_ PLB/β-Actin :0.26±0.12 vs 0.20±0.08, P =0.045),yet SERCA_2 mRNA was lower than PS group (0.48±0.10 vs 0.80±0.11, P <0.01). In CHF-T group, the mRNA levels of NCX_1 and SERCA_2 were just in the midst of the CHF-C and PS group, and had statistical significance respectively (all P <0.05). In CHF-C and CHF-T group, the protein levels of NCX_1 were 1.141±0.047 and 1.074±0.081 times PS group, respectively (both P <0.05), and SERCA_2 protein levels were respectively 0.803±0.110 and 0.893±0.084 times as high as in PS group (both P <0.05). The protein expression of NCX_1 and SERCA_2 were also different between CHF-C and CHF-T groups (both P <0.05).Conclusion

关 键 词：培哚普利 心力衰竭 大鼠 心肌细胞 钙瞬变 调控蛋白 

分 类 号：R541.6[医药卫生—心血管疾病] R972[医药卫生—内科学]