多二磷酸腺苷一核糖聚合酶在大鼠心肌缺血再灌注损伤中的作用及其对核转录因子κB活性和炎症因子表达的调节  

Poly （ADP-ribose） polymerase inhibition attenuates ischemia/reperfusion induced myocardial injuryin rat via reducing myocardial nuclear factor r,B activity

作　　者：宋兆峰[1] 杜波[1] 季晓平[2] 

机构地区：[1]山东省泰安市中心医院心内科,271000 [2]山东大学齐鲁医院心内科

出　　处：《中华心血管病杂志》2012年第12期997-1002,共6页Chinese Journal of Cardiology

基　　金：山东省自然科学基金（ZR2010HM069）;泰安市科技发展计划（20093077）

摘　　要：目的探讨多二磷酸腺苷-核糖聚合酶[Poly（ADP．ribose）polymerase，PARP]在大鼠心肌缺血再灌注（I／R）损伤中的作用，及其对核转录因子KB（NF—KB）活性和炎症因子表达的调节。方法将54只大鼠随机分为I／R组、I／R＋DPQ（PARP抑制剂）组和对照组。蛋白质免疫印迹法检测大鼠心肌中PARP蛋白的表达水平，硝基四氮唑蓝染色和末端脱氧核苷酸转移酶介导的dUTP缺口标记技术分别检测大鼠心肌梗死面积和心肌细胞凋亡的变化，电泳迁移率变更分析法检测大鼠心肌中NF—KB的活性及细胞间黏附分子-1（ICAM-1）、环氧化酶-2（COX-2）和基质金属蛋白酶．9（MMP-9）mRNA和蛋白的表达水平。结果（1）I／R组大鼠心肌组织中PARP蛋白表达水平显著高于对照组，I／R＋DPQ组低于I／R组（P均〈0．05）。（2）I／R＋DPQ组大鼠心肌梗死面积／左心室面积为（31．45±5．54）％，显著小于I／R组的（45．97±4．22）％（P〈0．05）。I／R＋DPQ组大鼠心肌细胞凋亡率为（23．0±3．8）％，显著低于I／R组的（34．0±6．2）％（P〈0．05）。（3）IZR组大鼠心肌组织中NF—KB的活性显著高于对照组，ICAM．1、COX．2和MMP-9mRNA和蛋白的表达水平亦均显著高于对照组，而I／R＋DPQ组大鼠心肌组织中上述因子的活性及表达水平均显著低于I／R组（P均〈0．05）。结论在大鼠心肌I／R过程中，PARP蛋白的表达水平明显增高，并通过增强NF—KB的活性和增加ICAM-1、COX．2及MMP-9mRNA和蛋白的表达水平造成心肌损伤。Objective To investigate the effect of Poly （ADP-ribose） polymerase （PARP） inhibition on ischemia/reperfusion （I/R） induced myocardial injury in rat and related mechanisms. Method Adult Wistar rats were randomly divided into sham-control （n = 18 ） , I/R （60 min ischemia followed by 180 rain reperfusion, n = 18 ） and I/R ＋ PARP inhibitor 3,4-dihydro-5- [ 4- （ 1-piperidinyl ） butoxy 1-1 （ 2H ） - isoquinolinone （DPQ）, 10 mg/kg, i.p. injection at 1 h before I/R （n = 18 ）. Myocardial expression of PARP, infarct size, and cardiomyocytes apoptosis were determined. Additionally, myocardial NF-KB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 at protein and mRNA level were detected. Result （ 1 ） Myocardial expression of PARP was significantly upregulated in I/R group compared to sham-control group, which could be significantly reduced by pretreatment with DPQ （ P 〈 0. 05 vs. I/R group）. （ 2 ） Infarct size [ （ 31.45 ± 5.54 ） % vs. （ 45.97 ±4. 22 ） % I and cardiomyocytes apoptosis （ 23.0 ± 3. 8 ） % vs. （ 34. 0 ± 6. 2 ） % ] were significantly reduced by pretreatment with DPQ （ all P 〈 O. 05 vs. I/R group）. （3） Pretreatment with DPQ also significantly decreased the NF-KB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 at both protein and mRNA level （ all P 〈 O. 05）. Conclusion The expression of PARP, NF-KB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9 are upregulated in I/R induced myocardial injury. PARP inhibitor DPQ could attenuate I/R induced myocardial injury through reducing NF-KB activity and the myocardial expressions of ICAM-1, COX-2 and MMP-9.

关 键 词：心肌再灌注损伤 聚ADP核糖聚合酶类 NF—KB 炎症介导素类 

分 类 号：R541[医药卫生—心血管疾病]