激活蛋白激酶C对离体兔心室电整复性及心律失常的影响

Activating protein kinase C enhances ventricular action potential duration restitution and increasearrhythmia susceptibility in Langendorff-perfused rabbit hearts

目的 探讨激活蛋白激酶C（PKC）对离体兔心室电整复性（APDR）及心律失常的影响。方法雄性新西兰大耳兔45只，随机分为对照组、PKC激活组（PMA组）和PKC抑制剂组（BIM组），每组15只。所有动物在整体心脏Langendorff灌流下进行离体电生理研究，分别记录和测量右心室基底部（RB）、右心室尖部（RA）、左心室基底部（LB）和左心室心尖部（LA）的单相动作电位（MAP）及有效不应期（ERP），并绘制电整复性曲线。运用Burst刺激法于RB、RA、LB和LA诱发室性心律失常。使用实时定量PCR技术检测上述4个部位PKC的mRNA表达量。结果PMA组心室各部位ERP、复极程度达到90％的时间（MAPD90）和ERP／MAPD90均较对照组小（P均〈0．01）；PMA组心室各部位APDR曲线最大斜率（Smax）均较对照组相同部位大（RB：1．22±0．23比0．65±0．19；RA：2．99±0．29比1．02±0．18：LB：1．84±0．21比0．85±0．12；LA：4．02±0．32比1．12±0．23，P均〈0．01）且与各部位PKC的mRNA表达量呈对应关系；PMA组动物心室各部位心律失常诱发率高于对照组；而BIM组上述各项指标与对照组相比差异均无统计学意义。结论激活PKC导致离体兔心室各部位APDR曲线Smax不均一性增大，为室性心律失常的发生提供条件。

±±±Objective To determine effects of activating protein kinase C （PKC） on ventricular action potential duration restitution （APDR） and Burst stimulus induced arrhythmia in Langendorff-perfused rabbit hearts. Methods Male rabbits were equally divided into three groups randomly： control group （Tyrode＇s solution perfusion）, PKC agonist phorbol-12-myristate-13- acetate （PMA, 100 nmol/L） group and PKC inhibitor bisindolylmaleimide （BIM, 500 nmol/L） group. Thirty minutes after perfusion, the monophasic action potential （MAP） and effective refractory period （ERP） were determined in right basal ventricle （RB） , right apex （ RA）, left basal ventricle （LB） and left apex （LA） of all the animals, and APDR curve was drawn. Burst stimulus method was used to induce ventricular arrhythmia in perfused rabbit hearts; Real-time PCR was used to detect the mRNA expression of PKC in four different areas of ventricle. Results Compared with the control group, the ERP, 90% of monophasic action potential duration （MAPDg0） and ERP/MAPDgo were significantly shortened （all P 〈 0. 01 ） , the max slopes （Sm±） of APDR curve were significantly steeper （RB： 1.22 ±0. 23 vs. 0. 65 ±0. 19; RA： 2. 99 ± 0. 29 vs. 1.02 ±-0. 18; LB： 1.84 ±0. 21 vs. 0. 85 ±0. 12; LA： 4. 02 ±0. 32 vs. 1.12 ±0. 23, all P 〈0. 01） and the incidences of ventricular arrhythmia were significantly increased in the PMA group. All parameters were similar between the BIM group and the control group （ all P 〉 0. 05 ）. Conclusion Activating PKC could enhance the max slopes of APDR curve at various ventricular areas and subsequently increase arrhythmia susceptibility in Langendorff-perfused rabbit hearts.