匹那地尔对大鼠缺血心肌钙调控的作用  

Effect of pinacidil on rat myocardial calcium regulation

作　　者：林茹[1] 康曼丽[1] 曹春梅[2] 夏强[2] 舒强[1] 张泽伟[1] 

机构地区：[1]浙江大学医学院附属儿童医院胸心外科,浙江杭州310003 [2]浙江大学医学院生理学教研室,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2003年第3期215-218,共4页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省教育厅科研基金 (4 910 4 0 - G2 0 0 4 5 );浙江省科技厅科研基金 (2 0 0 3C330 2 2 )资助项目

摘　　要：目的 :探讨大鼠缺血心肌再灌注 (I- R)损伤的钙调控机制及匹那地尔对心肌 I- R损伤的保护作用机理。方法 :取 SD大鼠 ,心室肌细胞酶解分离 ,心肌细胞静息 1～ 2 h后随机分为 4组 :对照组、高钾停搏液组、匹那地尔强化组、格列苯脲拮抗组。 4组细胞在 2 4℃下保存 2 h后 ,复氧、复灌 2 0 min同时测定 [Ca2 + ]i 瞬态变化、肌浆网内贮钙释放功能。结果 :经匹那地尔强化处理的心肌细胞在 I- R过程中 [Ca2 + ]i 瞬态变化恢复率明显高于高钾停搏液组 (90 .2 7%～ 95 .5 7% vs6 7.0 5 %～ 80 .11% ,P<0 .0 1)。肌浆网内贮钙释放能力 (173.15 %± 2 6 .0 1% )明显高于高钾停搏液组 (112 .0 0 %± 16 .93% ) (P<0 .0 1)。经匹那地尔强化处理的心肌细胞在咖啡因诱导的钙释放后 ,胞内钙离子浓度从高水平回复到舒张末静息水平的时间为 (3.2 0± 0 .71) ms,显著短于高钾停搏液组 (3.93± 0 .4 6 ) ms(P<0 .0 5 )和对照组 (4 .6 8± 0 .77) ms(P<0 .0 1)。结论 :匹那地尔通过肌浆网和细胞膜 Na+ /Ca2 +交换体功能来调节钙瞬态变化 ,减少细胞内钙超载使心肌细胞在 I- R过程中保持较好的钙调控功能。Objective: To understand the effect of pinacidil on rat myocardial Ca 2+ regulation.Methods: After baseline measurement and a period of equilibrium , myocytes were randomly allocated to one of 4 treatment groups: Control group (8 myocytes): incubation in Lactate Ringer's solution at 24℃ for 2 hours; K group (8 myocytes): incubation in Lactate Ringer's solution containing 16 mmol/L potassium at 24℃ for 2 hours; K+P group (8 myocytes): incubation in Lactate Ringer's solution containing potassium 16 mmol/L and pinacidil 50 μmol/L at 24 ℃ for 2 hours; K+P+G group (8 myocytes): incubation in Lactate Ringer's solution containing potassium 16 mmol/L, pinacidil 50 μmol/L and glibenclamide 10 μmol/L at 24℃ for 2 hours. After each incubation, myocytes were resuspended in cell culture media at the same temperature and intracellular i and SR Ca 2+ release were measured. Results: The amplitude percent of i transient evoked by electrical stimulation in the K group was significantly decreased to 67.05%～80.11% compared to 90.27%～95.57% in the K+P group during reperfusion after ischemia (P<0.01). The percent amplitude of the i transient evoked by the rapid application of 10 mmol caffeine in the K group myocyte was approximately 112.00%±16.93% compared with that of the i transient evoked by electrical stimulation. However, in the K+P group myocyte the peak amplitude of the caffeine-induced Ca 2+ release was 173.15%±26.01% compared with electrical stimulation(P<0.01). The duration of transient evoked by caffeine in K+P group (3.20±0.71)ms was signifcantly shorter than that in K group(3.93±0.46) ms (P<0.05).Conclusion: Cardioplegic arrest with simultaneous activation of KATP channels preserves rat myocardial Ca 2+ by inducing sarcoplasmic reticulum Ca 2+ release and by alteration of Na +-Ca 2+exchanger to better maintain i homeostasis.

关 键 词：心肌缺血 再灌注损伤 钙调控机制 匹那地尔 

分 类 号：R541[医药卫生—心血管疾病]