摘要
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10min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40min;P组灌注充氧K-14液10min后,灌注10μmol/L充氧吡那地尔30min;G组灌注10μmol/L充氧格列本脲10min后,再灌注10μmol/L充氧吡那地尔30min。随后I/R组、P组和G组行全心缺血40min,再灌注充氧K—H液。I/R组、P组和G组分别于心率平稳10min、再灌注30、60min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120min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、ICA-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。
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); ⅡI/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 momated 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 10μmol/L pinacidil for 30 min and group G received perfusion with 37℃ oxygenated 10 gmol/L glibenclamide 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-Ⅳfor determinatiort 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-α 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. Conchtsion Pinacidil preconditioning can protect myocardium against inflammatory response induced by I/R by opening ATP-sensitive K^+ channel which can be blocked by glibenclamide.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2008年第3期224-227,共4页
Chinese Journal of Anesthesiology
基金
贵州省优秀青年人才培养基金资助项目(2002-0217)
关键词
吡那地尔
心肌再灌注损伤
炎症
Pinacidil
Myocardial repeffusion injury
Inflammation