胸段硬膜外阻滞对急性心肌梗塞大鼠心肌多聚ADP核糖聚合酶表达的影响

Effect of thoracic epidural block on the expression of poly （ADP-ribose） polymerase in cardiomyocytes in rats with acute myocardial infarct

目的 研究胸段硬膜外阻滞（TEB）对急性心肌梗塞（AMI）大鼠心肌多聚ADP核糖聚合酶（PARP）（一种DNA修复蛋白）表达的影响。方法 65只健康雄性Wistar大鼠，随机分为3组：正常对照组（C组，n=5）、AMI组（n=30）、TEB组（n=30）。采用结扎大鼠左冠状动脉前降支制备AMI模型。TEB组行T4，5硬膜外置管，在制备AMI模型成功后，白天硬膜外注射1％利多卡因50μl，1次／2 h。AMI组和TEB组分别于结扎左冠状动脉后2 h（T1）、4 h（T2）、6 h（T3）、1周（T4）、4周（T5）、8周（T6）随机处死5只大鼠，测定坏死心肌组织PARP和DNA片段化水平。结果 AMI组、TEB组T2，3时检测到85 kD PARP，与C组比较，AMI组、TEB组T2，3时85 kD PARP水平增强（P〈0．05）;与AMI组比较，TEB组T2，3时85 kD PARP水平降低（P〈0．05），AMI组和TEB组T4-6时均未检测到85 kD PARP。AMI组T2时检测到DNA片段化，T3时其水平明显增强，TEB组T3时检测到DNA片段化，AMI和TEB组T4-6时均未检测到DNA片段化。结论 TEB可在一定程度上抑制AMI大鼠早期心肌PARP的降解，促进心肌细胞DNA的修复。

Objective To investigate the effect of thoracic epidural block （TEB） on the expression of poly （ADP-ribose） polymerase （PARP） （a DNA repair protein） in cardiomyocytes in a rat model of acute myocardial infarct （AMI）. Methods Sixty-five male Wistar rats weighing 200-250 g were randomly divided into 3 groups： group 1 control （ n = 5） ; group Ⅱ AMI （ n = 30） and group Ⅲ TEB （ n = 30）. AMI was produced by ligation of the left anterior descending （LAD） artery and confirmed by elevation of ST segment on ECG in group Ⅱ and Ⅲ. In group Ⅲ an epidural catheter was inserted at T4-5 interspace into epidural space and advanced cephalad for 2-3 mm. 1% lidocaine 50 μl was injected over 15 s every 2 h during the daytime after AMI was produced. Five rats each were killed at 2 h （T1）, 4 h （T2）, 6 h （T3）, 1 w （T4）, 4 w （T5） and 8 w （T6） after ligation of LAD artery in group Ⅱ and Ⅲ . Their hearts were immediately removed. Myocardial specimens were obtained from infarct area for determination of PARP expression by Western blot. The level of DNA fragmentation was detected by DNA ladder. Their temporal and sequence changes were observed. Results The 85 kD PARP level was detected at T2 and T3 in AMI and TEB groups and was significantly lower in TEB group than in AMI group. No PARP cleavage was found at T4-6 in both AMI and TEB groups. DNA fragmentation was found at T2 and was significantly increased at T3 in AMI group; while in TEB group DNA fragmentation was detected only at T3. No DNA fragmentation was found at T4-6 in both AMI and TEB groups. Conclusion TEB may inhibit the degradation of PARP and promote DNA repair in cardiomyocytes to some extent in the early stage of AMI in rats.