吡那地尔预处理对兔心脏缺血再灌注时心肌炎性反应的影响

目的 评价吡那地尔预处理对兔心脏缺血再灌注时心肌炎性反应的影响.方法 日本大耳白兔56只,随机分为4组:正常对照组(C组,n=8)、缺血再灌注组(I/R组,n=16)、吡那地尔预处理组(P组,n=16)和格列本脲组(G组,n=16).建立离体心脏Langendorff再灌注模型,灌注充氧K-H液,待心率平稳10 min时,C组取心肌组织,测定丙二醛(MDA)、补体C3a、细胞间粘附分子-1(ICAM-1)和细胞核NF-κBp65表达;I/R组继续灌注充氧K-H液40 min;P组灌注充氧K-H液10 min后,灌注10 μmol/L充氧吡那地尔30 min;G组灌注10 μmol/L充氧格列本脲10 min后,再灌注10 μmol/L充氧吡那地尔30min.随后I/R组、P组和G组行全心缺血40 min,再灌注充氧K-H液.I/R组、P组和G组分别于心率平稳10 min、再灌注30、60 min时取8个心脏,测定冠状静脉流出液中肌酸激酶(CK)活性和肿瘤坏死因子-α(TNF-α)浓度;再灌注60或120 min时测定心肌组织MDA、补体C3a、ICAM-1及细胞核NF-κBp65表达.结果 P组再灌注期间CK、TNF-α、MDA、补体C3a、ICAM-1和NF-κBp65水平均明显低于其他各组(P＜0.05).结论 吡那地尔预处理可减轻兔心脏缺血再灌注时心肌炎性反应,可能与ATP敏感性钾通道开放有关,从而对心肌产生保护作用.

Effect of pinacidil preconditioning on myocardial inflammatory response to ischemia-reperfusion of isolated rabbit heart

Objective To evaluate the effect of pinacidil preconditioning on myocardial inflammatory response to ischemia-reperfusion(I/R)of isolated rabbit heart.Methods Fifty-six Japanese long-ear white rabbits of both sexes weighing 1.8-2.2 kg were randomly divided into four groups:Ⅰ normal control group was subjected to no I/R(C,n=8);Ⅱ I/R group(n=16);Ⅲ pinacidil preconditioning group(P,n=16)and Ⅳ glibenclamide +pinacidil preconditioning group(G,n=16).The animals were given heparin 300 IU/kg iv before being killed by a blow on the head.The hearts were immediately removed and mounted in a Langendorff apparatus and perfused with 37℃ oxygenated Krebs-Hensleit(K-H)solution.Ischemia was induced by perfusion with 4℃ St Thomas cardioplegic solution in group I/R,P and G and maintained for 40 min followed by reperfusion with 37℃ oxygenated K-H solution.In group P received perfusion with 37℃ oxygenated 10 μmol/L pinacidil for 30 min and group G received perfusion with 37℃ oxygenated 10 μmol/L glibonclamide for 10 min and then 37℃ oxygenated 10 μmol/L pinacidil for 30 min before I/R.Eight hearts were retrieved in group C after 10 min perfusion with 37℃oxygenated K-H solution and at 60 and 120 min of reperfusion in group Ⅱ-Ⅳ for determination of MDA and complement 3a(C3a)level and ICAM-1 expression in myocardium and the ratio of cardiomyocytes with NF-κBp65 positive nucleus.Coronary sinus effluent was collected at 10 min post-preparation equilibration(baseline)and 30 and 60 min of reperfusion-for determination of CK activity and TNF-α concentration respectively.Results The CK activity and TNF-a concentration in coronary sinus effluent and the MDA and C3a level,and ICAM-1 expression in myocardium and the ratio of cardiomyocytes with NF-κBp65 positive nucleus were significantly lower in group P than in other 3 groups.Conclusion Pinacidil preconditioning can protect myocardium against inflammatoryresponse induced by I/R by opening ATP-sensitive K+ channel which can be blocked by glibenclamide.