中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2012年
12期
997-1002
,共6页
心肌再灌注损伤%聚ADP核糖聚合酶类%NF-κB%炎症介导素类
心肌再灌註損傷%聚ADP覈糖聚閤酶類%NF-κB%炎癥介導素類
심기재관주손상%취ADP핵당취합매류%NF-κB%염증개도소류
Myocardial reperfusion injury%Poly(ADP-ribose) polymerases%NF-kappa B%Inflammation mediators
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κB(NF-κB)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-κB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)I/R组大鼠心肌组织中NF-κB的活性显著高于对照组,ICAM-1、COX-2和MMP-9 mRNA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-κB的活性和增加ICAM-1、COX-2及MMP-9 mRNA和蛋白的表达水平造成心肌损伤.
目的 探討多二燐痠腺苷-覈糖聚閤酶[Poly(ADP-ribose)polymerase,PARP]在大鼠心肌缺血再灌註(I/R)損傷中的作用,及其對覈轉錄因子κB(NF-κB)活性和炎癥因子錶達的調節.方法 將54隻大鼠隨機分為I/R組、I/R+ DPQ(PARP抑製劑)組和對照組.蛋白質免疫印跡法檢測大鼠心肌中PARP蛋白的錶達水平,硝基四氮唑藍染色和末耑脫氧覈苷痠轉移酶介導的dUTP缺口標記技術分彆檢測大鼠心肌梗死麵積和心肌細胞凋亡的變化,電泳遷移率變更分析法檢測大鼠心肌中NF-κB的活性及細胞間黏附分子-1(ICAM-1)、環氧化酶-2(COX-2)和基質金屬蛋白酶-9(MMP-9) mRNA和蛋白的錶達水平.結果 (1)I/R組大鼠心肌組織中PARP蛋白錶達水平顯著高于對照組,I/R+ DPQ組低于I/R組(P均＜0.05).(2)I/R+ DPQ組大鼠心肌梗死麵積/左心室麵積為(31.45±5.54)％,顯著小于I/R組的(45.97±4.22)％(P＜0.05).I/R+ DPQ組大鼠心肌細胞凋亡率為(23.0±3.8)％,顯著低于I/R組的(34.0±6.2)％(P＜0.05).(3)I/R組大鼠心肌組織中NF-κB的活性顯著高于對照組,ICAM-1、COX-2和MMP-9 mRNA和蛋白的錶達水平亦均顯著高于對照組,而I/R+ DPQ組大鼠心肌組織中上述因子的活性及錶達水平均顯著低于I/R組(P均＜0.05).結論 在大鼠心肌I/R過程中,PARP蛋白的錶達水平明顯增高,併通過增彊NF-κB的活性和增加ICAM-1、COX-2及MMP-9 mRNA和蛋白的錶達水平造成心肌損傷.
목적 탐토다이린산선감-핵당취합매[Poly(ADP-ribose)polymerase,PARP]재대서심기결혈재관주(I/R)손상중적작용,급기대핵전록인자κB(NF-κB)활성화염증인자표체적조절.방법 장54지대서수궤분위I/R조、I/R+ DPQ(PARP억제제)조화대조조.단백질면역인적법검측대서심기중PARP단백적표체수평,초기사담서람염색화말단탈양핵감산전이매개도적dUTP결구표기기술분별검측대서심기경사면적화심기세포조망적변화,전영천이솔변경분석법검측대서심기중NF-κB적활성급세포간점부분자-1(ICAM-1)、배양화매-2(COX-2)화기질금속단백매-9(MMP-9) mRNA화단백적표체수평.결과 (1)I/R조대서심기조직중PARP단백표체수평현저고우대조조,I/R+ DPQ조저우I/R조(P균＜0.05).(2)I/R+ DPQ조대서심기경사면적/좌심실면적위(31.45±5.54)％,현저소우I/R조적(45.97±4.22)％(P＜0.05).I/R+ DPQ조대서심기세포조망솔위(23.0±3.8)％,현저저우I/R조적(34.0±6.2)％(P＜0.05).(3)I/R조대서심기조직중NF-κB적활성현저고우대조조,ICAM-1、COX-2화MMP-9 mRNA화단백적표체수평역균현저고우대조조,이I/R+ DPQ조대서심기조직중상술인자적활성급표체수평균현저저우I/R조(P균＜0.05).결론 재대서심기I/R과정중,PARP단백적표체수평명현증고,병통과증강NF-κB적활성화증가ICAM-1、COX-2급MMP-9 mRNA화단백적표체수평조성심기손상.
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 min reperfusion,n =18) and I/R + PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl) butoxy]-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-κB 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) ％] and cardiomyocytes apoptosis [(23.0 ± 3.8) ％ vs.(34.0 ± 6.2) ％] were significantly reduced by pretreatment with DPQ (all P ＜ 0.05 vs.I/R group).(3) Pretreatment with DPQ also significantly decreased the NF-κB activity and the myocardial expressions of ICAM-1,COX-2 and MMP-9 at both protein and mRNA level (all P ＜ 0.05).Conclusion The expression of PARP,NF-κB 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-κB activity and the myocardial expressions of ICAM-1,COX-2 and MMP-9.
