缺血后处理对兔缺血再灌注损伤心肌细胞NF-κB及ICAM-1表达的影响
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摘要
目的:建立缺血后处理动物模型,并探讨缺血后处理对兔心肌缺血再灌注损伤保护作用的可能机制。
方法:健康成年新西兰兔40只随机分为三组:对照组(假手术组)、缺血再灌注组(I/R组)、缺血后处理组(IPTC组)。每组按再灌注时间长短再分为四亚组:0.5小时组、1小时组、2小时组、3小时组。对照组(假手术组)8只,不同时间点每亚组2只;I/R组16只,不同时间点每亚组4只;IPTC组16只,不同时间点每亚组4只。假手术组:开胸暴露心脏后找到左冠前降支(LAD)穿线做套环,但不收紧结扎线;I/R组:收紧结扎线,LAD缺血30min,再灌注0.5-3小时;IPTC组:LAD缺血30min后给予30秒再灌注、再缺血,重复4次,然后再灌注0.5-3小时。建立动物模型时,分别于缺血前、结扎30min后、开放1h及开放3h四个时间点抽血检测肌酸激酶(CK)、肌钙蛋白I(cTnI),将缺血心肌、梗死心肌分开称重。处死试验动物后,取缺血再灌注区的心肌组织以免疫组织化学法检测NF-κB和ICAM-1的表达情况。运用全自动图像分析系统对免疫组化结果进行分析处理,分别比较假手术组、I/R组和IPTC组不同时间点NF-κB、ICAM-1的表达数值,以SPSS11.5统计软件进行统计学分析。分析NF-κB和ICAM-1的表达相关性。
结果:1.CK、cTnI及心梗面积的比较:I/R组与对照组相比再灌注1小时后CK、cTnI明显升高(P＜0.05),IPTC组与I/R组相比1小时后CK、cTnI明显降低(P＜0.05);IPTC组与I/R组相比,心梗面积明显缩小(P＜0.05)。2.NF-κB的表达情况:假手术组心肌细胞未见NF-κBp65阳性表达;I/R组NF-κBp65表达明显增强(P＜0.01),且表达强度随时间逐渐增高,再灌注2小时达高峰,随后下降;IPTC组NF-κBp65表达较I/R组明显下降(P＜0.01)。3.ICAM-1的表达情况:假手术组心肌细胞未见ICAM-1阳性表达;I/R组ICAM-1表达明显增强(P＜0.01),且表达强度随时间逐渐增高,再灌注3小时表达最强;IPTC组ICAM-1表达较I/R组明显下降(P＜0.01);3.NF-κB表达与ICAM-1表达呈现同步性,而NF-κB的表达高峰时间先于ICAM-1的表达。
结论:1.缺血后处理能抑制缺血再灌注心肌细胞的NF-κB和ICAM-1表达;2.NF-κB可能通过调控ICAM-1的表达在缺血再灌注损伤中发挥作用。
Objective : To investigate the possible mechanisms of ischemic/refusion postconditioning's protetive effects on myocardium in rabbits.
Methods: 40 adult New Zealand rabbits weighing 1.5-2.0Kg were divided into three groups: control group(sham operation group), ischemic/reperfusion group(I/R group) and ischemic postconditioning group(IPTC group). Each group was divided into four subsets according to reperfusion time course: 0.5h subset, 1h subset, 2h subset and 3h subset. Control group(sham operation group) contains 8 rabbits : 2 for each subset. Ischemia/reperfusion group contains 16 rabbits: 4 for each subset. Ischemic postconditioning group contains 16 rabbits: 4 for each subset. For sham operation group, expose heart by surgery and find left anterior descending (LAD) coronary artery, and then braid to make a ringer but remain the silk untensioned; For ischemia/reperfusion group, contract the ringer to block LAD for 30 min and then reperfusion for 0.5-3h; For ischemic postconditioning group, block LAD for 30min and then begin a cycle with reperfusion for 30 seconds and block for 30 seconds, repeat the cycle four times, and then reperfusion for 0.5-3h. Take the ischemia/reperfusion area myocardium to detect NF-κB and ICAM-1 expression by immunohistochemistry methods. Compare the NF-κB and ICAM-1 expression postive unit data by KONTRON IBAS 2.5 automatic image analyze system. Analyze the data and the correlation between NF-κB and ICAM-1 with SPSS 11.5.
Results: 1. CK、cTnI and infarct size: increases remarkably in I/R group compared with control group (P<0.05) ; CK and cTnI decreases remarkably in IPTC group compared with I/R group (P<0.05 ) ;Infarct size decreases remarkably in IPTC group compared with I/R group (P<0.05 ) . 2. NF-κB: sham operation group does not express NF-κBp65; while ischemia/reperfusion group demonstrates distinct postive expression (P<0.01), and the postive unit is dependent on reperfusion time cousre. It reaches the maximum by reperfusion 2h and declines then .As for ischemic postconditioning group, the NF-κBp65 expression is distinctly decreased compared with ischemia/reperfusion group (P<0.01). 3. ICAM-1: sham operation group remains negtive expression; while ischemia/reperfusion group ICAM-1 expression increases distinctly (P<0.01). Also the postive unit is dependent on reperfusion time cousre and it reaches the maxium by reperfusion 3h. Ischemic postconditioning group demonstrates the ICAM-1 expression decreases remarkably compared with ischemia/reperfusion group (P<0.01). 4.The expession postive unit between NF-κB and ICAM-1 appears synchronism, and the NF-κB maximum expression time is prior to ICAM-1.
Conclusions: 1.Ischemic postconditioning inhibits the expression of NF-κB and ICAM-1 in ischemia/reperfusion myocardium; 2. NF-κB might regulate the expression of ICAM-1 in ischemia/reperfusion injury.
方法:健康成年新西兰兔40只随机分为三组:对照组(假手术组)、缺血再灌注组(I/R组)、缺血后处理组(IPTC组)。每组按再灌注时间长短再分为四亚组:0.5小时组、1小时组、2小时组、3小时组。对照组(假手术组)8只,不同时间点每亚组2只;I/R组16只,不同时间点每亚组4只;IPTC组16只,不同时间点每亚组4只。假手术组:开胸暴露心脏后找到左冠前降支(LAD)穿线做套环,但不收紧结扎线;I/R组:收紧结扎线,LAD缺血30min,再灌注0.5-3小时;IPTC组:LAD缺血30min后给予30秒再灌注、再缺血,重复4次,然后再灌注0.5-3小时。建立动物模型时,分别于缺血前、结扎30min后、开放1h及开放3h四个时间点抽血检测肌酸激酶(CK)、肌钙蛋白I(cTnI),将缺血心肌、梗死心肌分开称重。处死试验动物后,取缺血再灌注区的心肌组织以免疫组织化学法检测NF-κB和ICAM-1的表达情况。运用全自动图像分析系统对免疫组化结果进行分析处理,分别比较假手术组、I/R组和IPTC组不同时间点NF-κB、ICAM-1的表达数值,以SPSS11.5统计软件进行统计学分析。分析NF-κB和ICAM-1的表达相关性。
结果:1.CK、cTnI及心梗面积的比较:I/R组与对照组相比再灌注1小时后CK、cTnI明显升高(P＜0.05),IPTC组与I/R组相比1小时后CK、cTnI明显降低(P＜0.05);IPTC组与I/R组相比,心梗面积明显缩小(P＜0.05)。2.NF-κB的表达情况:假手术组心肌细胞未见NF-κBp65阳性表达;I/R组NF-κBp65表达明显增强(P＜0.01),且表达强度随时间逐渐增高,再灌注2小时达高峰,随后下降;IPTC组NF-κBp65表达较I/R组明显下降(P＜0.01)。3.ICAM-1的表达情况:假手术组心肌细胞未见ICAM-1阳性表达;I/R组ICAM-1表达明显增强(P＜0.01),且表达强度随时间逐渐增高,再灌注3小时表达最强;IPTC组ICAM-1表达较I/R组明显下降(P＜0.01);3.NF-κB表达与ICAM-1表达呈现同步性,而NF-κB的表达高峰时间先于ICAM-1的表达。
结论:1.缺血后处理能抑制缺血再灌注心肌细胞的NF-κB和ICAM-1表达;2.NF-κB可能通过调控ICAM-1的表达在缺血再灌注损伤中发挥作用。
Objective : To investigate the possible mechanisms of ischemic/refusion postconditioning's protetive effects on myocardium in rabbits.
Methods: 40 adult New Zealand rabbits weighing 1.5-2.0Kg were divided into three groups: control group(sham operation group), ischemic/reperfusion group(I/R group) and ischemic postconditioning group(IPTC group). Each group was divided into four subsets according to reperfusion time course: 0.5h subset, 1h subset, 2h subset and 3h subset. Control group(sham operation group) contains 8 rabbits : 2 for each subset. Ischemia/reperfusion group contains 16 rabbits: 4 for each subset. Ischemic postconditioning group contains 16 rabbits: 4 for each subset. For sham operation group, expose heart by surgery and find left anterior descending (LAD) coronary artery, and then braid to make a ringer but remain the silk untensioned; For ischemia/reperfusion group, contract the ringer to block LAD for 30 min and then reperfusion for 0.5-3h; For ischemic postconditioning group, block LAD for 30min and then begin a cycle with reperfusion for 30 seconds and block for 30 seconds, repeat the cycle four times, and then reperfusion for 0.5-3h. Take the ischemia/reperfusion area myocardium to detect NF-κB and ICAM-1 expression by immunohistochemistry methods. Compare the NF-κB and ICAM-1 expression postive unit data by KONTRON IBAS 2.5 automatic image analyze system. Analyze the data and the correlation between NF-κB and ICAM-1 with SPSS 11.5.
Results: 1. CK、cTnI and infarct size: increases remarkably in I/R group compared with control group (P<0.05) ; CK and cTnI decreases remarkably in IPTC group compared with I/R group (P<0.05 ) ;Infarct size decreases remarkably in IPTC group compared with I/R group (P<0.05 ) . 2. NF-κB: sham operation group does not express NF-κBp65; while ischemia/reperfusion group demonstrates distinct postive expression (P<0.01), and the postive unit is dependent on reperfusion time cousre. It reaches the maximum by reperfusion 2h and declines then .As for ischemic postconditioning group, the NF-κBp65 expression is distinctly decreased compared with ischemia/reperfusion group (P<0.01). 3. ICAM-1: sham operation group remains negtive expression; while ischemia/reperfusion group ICAM-1 expression increases distinctly (P<0.01). Also the postive unit is dependent on reperfusion time cousre and it reaches the maxium by reperfusion 3h. Ischemic postconditioning group demonstrates the ICAM-1 expression decreases remarkably compared with ischemia/reperfusion group (P<0.01). 4.The expession postive unit between NF-κB and ICAM-1 appears synchronism, and the NF-κB maximum expression time is prior to ICAM-1.
Conclusions: 1.Ischemic postconditioning inhibits the expression of NF-κB and ICAM-1 in ischemia/reperfusion myocardium; 2. NF-κB might regulate the expression of ICAM-1 in ischemia/reperfusion injury.
引文
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