大鼠心肌缺血再灌注早期PARP-1的表达及其抑制剂3-AB对心肌梗死面积的影响
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PARP-1 Expression and the Effects of 3-Aminobenzamide on Infarction Area of Rats During Early Stage of Heart Ischemia Reperfusion Injury
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    摘要:

    目的 探讨1型多聚ADP核糖聚合酶(PARP-1)在大鼠心肌缺血再灌注损伤早期心肌组织中的蛋白表达,观察其抑制剂3-氨基苯甲酰胺(3-AB)对心肌梗死面积的影响。方法 将164只大鼠随机分为:(1)手术组:又分7个小组,每组12只大鼠;(2)假手术组:又分7个小组,每组6只大鼠;(3)手术干预组(n=14);(4)手术对照组(n=12);(5)假手术干预组(n=6);(6)假手术对照组(n=6)。手术组:结扎冠状动脉左前降支近端45 min,打开系拌,建立心肌缺血再灌注损伤模型,分别于再灌注15 min、30 min、1 h、2 h、4 h、6 h、24 h各时间点处死大鼠,检测各时间点心肌组织PARP-1的表达。假手术组:开胸,在冠状动脉左前降支近端穿线但不结扎,分别于与缺血再灌注组相同各时间点(1 h、1 h 15 min、1 h 45 min、2 h 45 min、4 h 45 min、6 h 45 min、24 h 45 min)相同方法检测心肌组织PARP-1的表达。手术干预组:建立缺血再灌注模型,分别于再灌注前15 min及再灌注后45 min给予3-AB(20 mg/kg,静脉注射),于再灌注2 h处死大鼠,然后检测心肌组织PARP-1的表达(n=8),及心肌梗死面积(n=6)。手术对照组:建立缺血再灌注模型,分别于再灌注前15 min及再灌注后45 min给予等体积生理盐水静脉注射,用相同方法检测心肌组织PARP-1的表达(n=6)及心肌梗死面积(n=6)。结果 手术组于再灌注不同时间点(15 min、30 min、1 h、2 h、4 h、6 h、24 h)PARP-1表达灰度值(分别为176±7、180±8、190±9、207±15、198±13、196±9、190±5)与假手术组比较有显著差异(P<0.05)。手术干预组灰度值(171±7)与手术对照组灰度值(205±17)比较有显著差异(P<0.05)。手术干预组梗死面积(20%±2%)与手术对照组(33%±4%)比较有显著差异(P<0.05)。结论 心肌缺血再灌注早期心肌组织中PARP-1有明显表达,并呈动态变化,再灌注2 h最明显。3-AB明显抑制PARP-1表达,减小心肌梗死面积。有效抑制心肌缺血再灌注早期PARP-1表达可以减轻再灌注心肌损伤,保护心肌。

    Abstract:

    Aim To investigate the expression of poly ADP-ribose polymerase-1 (PARP-1) and to observe the effect of myocardial infarct size after the application of PARP-1 inhibitor 3-aminobenzamid (3-AB) in the early stage of my ocardial ischemia reperfusion (IR)in rat. Methods Rats (n=164) were randomly divided into 6 groups: operation groups including operation 15 min, 30 min, 1 h, 2 h, 4 h, 6 h and 24 h group (12 rats in each group), sham groups including sham 15 min, 30 min, 1 h, 2 h, 4 h, 6 h and 24 h group (6 rats in each group), operation drug group (n=14), operation saline group (n=12), sham drug group (n=6), sham saline group (n=6). The left anterior descending coronary artery (LAD) was ligated for 45 min and reperfused for different time of 15 min, 30 min, 1 h, 2 h, 4 h, 6 h and 24 h, IR model was set up, then the rats were killed, and the expression of PARP-1 in myocardial tissue was detected. Sham group animals received all the surgical procedures described previously, but the LAD was not tied. Drug of PARP inhibitor 3-AB (20 mg/kg, iv) was given to operation drug group and sham drug group and the equal volume of saline was given to operation saline group and sham saline group at 30 min after thoracotomy and 45 min after reperfusion, then the expression of PARP-1 in myocardial tissue and the infarct size were detected. Results The levels of PARP-1 in operation groups were obviously higher than those in sham groups (P<0.05). The level of PARP-1 in operation drug group was obviously lower than that in operation saline group (P<0.05). Infarct size in operation drug group and in operation saline group after reperfusion 2 hour was obviously different (P<0.05). Conclusions The content of PARP-1 gradually increased and dynamically changed in the early stage of myocardial ischemia reperfusion. Content of PARP-1 in myocardial after reperfusion for 2 hours had the most obvious expression. Drug of 3-AB obviously inhibited the level of PARP-1, decreased ischemia reperfusion injury and reduced infarct size. Actively using inhibitors of PARP-1 is significantly important in the early stage of myocardial ischemia reperfusion injury.

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邹吉丽,尹照萍,张利群,王永权,齐国先.大鼠心肌缺血再灌注早期PARP-1的表达及其抑制剂3-AB对心肌梗死面积的影响[J].中国动脉硬化杂志,2013,21(06):497~502.

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  • 收稿日期:2012-11-09
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