吡那地尔超极化停搏对大鼠离体心脏蛋白激酶C及热休克蛋白70的影响

Effects of pinacidil hyperpolarized arrest on protein kinase C and heat shock protein 70 in myocardium of isolated rat heart

目的探讨吡那地尔超极化停搏对大鼠离体心脏蛋白激酶C（PKC）ε及热休克蛋白70 （HSP70）的影响。方法成年雄性SD大鼠,成功建立Langendorff离体再灌注模型的32个心脏,随机分为4组（n=8）：自然停搏组（A组）、St.Thomas组（B组）、吡那地尔超极化组（C组）和白屈菜赤碱组（D组）。A组、B组和C组K-H液平衡灌注15min后,A组停止灌注,B组灌注St.Thomas停搏液,C组灌注超极化停搏液;D组K-H液平衡灌注10min后,白屈菜赤碱液灌注5min,再灌注超极化停搏液。记录各组平衡灌注15min和再灌注20min时冠脉流量（CF）、心率（HR）、左室发展压（LVDP）、左室收缩峰压（LVSP）和左室压力瞬时最大变化率（dp/dtmax）;再灌注30min时测定心肌膜性PKCε和HSP70的表达。结果与K-H液平衡灌注15min时相比,再灌注20min时A组、B组和D组CF、HR、LVSP、LVDP及dp/dtmax降低（P〈0.05）;与C组相比,其余各组再灌注20min时CF、HR、LVSP、LVDP及dp/dtmax降低,膜性PKCε和HSP70的表达下调（P〈0.05）。结论吡那地尔超极化停搏通过上调膜性PKCε和HSP70表达,促进大鼠心肌缺血再灌注时心功能恢复。

Objective To investigate the effects of pinacidil hyperpolarized arrest on protein kinase C epsilon （PKCε） and heat shock protein 70 （HSP70） in myoeardium of isolated rat hearts.Methods Male SD rats weighing 250-300 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital sodium. Their hearts were excised. The aorta was eannulated. The hearts were retrogradely perfused with an oxygenated K-H solution at a pressure of 8.8 kPa in a Langendorff apparatus. Left ventrieular developed pressure （LVDP） was measured from a fluid filled latex balloon in the left ventricle. Thirty-two isolated hearts were randomly divided into 4 groups （ n = 8 each） ： group A natural arrest; group B St. Thomas; group C pinaeidil and group D ehelerythrine. The isolated hearts stopped beating naturally in group A. Cardiac arrest was induced with St. Thomas eardioplegic solution in group B or pinacidil hyperpolarized eardioplegic solution in group C. In group D the hearts were perfused with ehelerythrine （ 10 μmol/L ） for 5 min followed by pinaeidil perfusion. Coronary flow （CF）, HR, LVDP, left ventrieular systolic prossure （LVSP） and dp/dt were measured after 15 min stabilization before cardiac arrest and at 20 min of reperfusion. The expression of myocardial membranous PKCe and HSP70 was determined at 30 min of reperfusion. Results CF, HR, LVDP, LVSP and dp/dtmax recovered well at 20 min of reperfusion and were not significantly different from the baseline values before isehemia in group C, but were significantly decreased at 20 min of reperfusion as compared with the baseline values in group A, B and D. Tbe expression of membranous PKCe and HSP70 was significantly higher at 30 min of reperfusion in group C than in group A, B and D. Conclusion Hyperpolarized arrest induced by pinaeidil can better protect cardiac function than depolarized arrest by increasing expression of membranous PKCe and HSP70.