吡那地尔超极化停搏对大鼠离体心脏p38MAPK的影响

Effects of pinacidil hyperpolarization arrest on p38 mitogen-activited protein kinase in isolated rat hearts

目的探讨吡那地尔超极化停搏对大鼠离体心脏p38丝裂原活化蛋白激酶(p38MAPK)的影响。方法成年雄性SD大鼠随机分为四组:自然停搏组(A组)、St.Thoma液停搏组(B组)、吡那地尔超极化液停搏组(C组)和SB203580液停搏组(D组),每组8只。采用Langen-dorff离体心脏灌注模型,检测冠脉流量(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)、心肌磷酸化p38MAPK和非磷酸化p38MAPK的表达。结果与K-H液平衡灌注15min时比较,再灌注20min时,A组、B组、D组CF、HR、LVSP、LVDP及dp/dtmax降低(P<0.05)。与C组比较,A组、B组、D组再灌注20min时CF、HR、LVSP、LVDP及dp/dtmax降低,再灌注30min时磷酸化p38MAPK表达下调(P<0.05),非磷酸化p38MAPK表达上调(P<0.05)。结论磷酸化p38MAPK介导了吡那地尔超极化停搏对大鼠离体心脏的保护,促进大鼠心肌缺血-再灌注时心功能恢复。

Objective To investigate the effects of pinacidil hyperpolarization arrest on p38 mitogen-activited protein kinase （p38MAPK） using a isolated rat heart. Methods The male SD rats were randomly divided into 4 groups of A（natural arrest）, B（arrest with St. Thomas solution）, C （arrest with pinacidil hyperpolarization solution） and D（arrest with SB203580 solution） with 8 rats each. Langendorff reperfusion model was established. Coronary flow （CF）, heart rate （HR）, left ventricular developed pressure （LVI）P）, left ventricular systolic pressure （LVSP） and the maximum rate of pressure rise （dp/dtmax） were measured and the myocardial phosphorylated and non- phosphorylated p38MAPK expressions were determined. Results Compared with the cardiac function after 15 rain K-H perfuion, the CF, HR, LVDP, LVSP and dp/dtmax at 20 min of reperfusion reduced in groups of A,B and D. Compared with group C, the CF, HR, LVDP, LVSP and dp/dmax at 20 min of reperfusion reduced and phosphorylated p38MAPK expression down-regulated （P〈0. 05）, but non-phosphorylated one up-regulated in groups of A, B and D（P〈0. 05）. Conclusion Phosphorylated p38MAPK mediates the protective effects of pinacidil hyperpolarization arrest on isolated rat hearts and promotes the revcovery of cardiac function of ischemia-reperfusion rat hearts.