摘要
目的观察苯那普利后处理对离体大鼠心肌缺血再灌注(I/R)损伤的保护作用,初步探讨其可能的作用机制。方法应用Langendroff离体灌流装置,采用完全停灌复灌方法制作离体大鼠心肌缺血再灌注模型。32只SD大鼠随机等分为4组:对照组、I/R组、缺血预处理组和苯那普利后处理组。测定各组稳灌20min和再灌60min时的冠脉流量,改良亮绿变色酸法(GCA)观察心肌损害程度,免疫组化法检测心肌组织中核因子-κB(NF-κB)和肿瘤坏死因子(TNF-α)的表达。结果与对照组比,I/R组,再灌注60min时的冠脉流量减少(P<0.01),心肌损害程度增加(P<0.01),免疫组织化学染色可见NF-κB蛋白表达显著增强且主要表达在心肌细胞核(P<0.01),TNF-α主要表达在心肌细胞胞质,呈强阳性。与I/R组相比,苯那普利后处理组再灌注60min时的冠脉流量增多[(4.3±0.4)ml/min和(3.5±0.5)ml/min,P<0.05],GCA染色心肌变性减轻,阳性率减低(14%±7%和40%±7%,P<0.01),NF-κB表达减少(34.8%±4.7%和49.3%±9.7%,P<0.05),TNF-α表达为弱阳性。苯那普利后处理组和预处理组相比较,差异无统计学意义(P>0.05)。结论苯那普利后处理对缺血再灌注心肌具有保护作用,其机制可能与苯那普利后处理抑制NF-κB活性,减少TNF-α的表达有关。
Objective To observe the protective effects of benazepril postconditioning during ischemia- reperfusion (I/R) in isolated rats hearts, and investigate the possible mechanism. Methods Thirty-two male Sprague-Dawley rats were isolated and perfused using the Langendorff mode with modified Kreb-Henseleit (KH) buffer and were randomly assigned into four groups: control group,I/R group, Preconditioning group, benazepril postconditioning group. The coronary flow was measured at minutes of perfusion 20 min and reperfusion 60 min, myocardial infarction size was examined by Gonori chromotropic acid staining (GCA) .The NF-κB and TNF-α were investigated by immunohistochemical technique. Results Compared with control, I/R caused a marked increase in the infarction size(P〈0.01 )and the expression of NF-κB (P〈0.01),decreased the coronary effluent at 60 min of reperfusion (P〈0.01).The expression of TNF-α was strong positive reaction in I/R group. Compared with I/R group,benazepril postconditioning increased the coronary effluent at 60 min of reperfusion[ (4.3±0.4)ml/min vs (3.5±0.5)ml/ min,P〈0.05), decreased the infarction size (14%±7% vs 40%±7%,P〈0.01 )and the expression of NF-κB (34.8%±4.7% vs 49.3%±9.7% ,P〈0.05).The expression of TNF-α was weak positive reaction in benazepril postconditioning group. There was no difference between benazepril postconditioning group and preconditioning group (P〉0.05). Conclusion Benazepril postconditioning induces cardioprotection associated with down-regulated NF-κB activation and the expression of TNF-α after ischemia-reperfusion in isolated rats.
出处
《中国心血管病研究》
CAS
2008年第4期294-297,共4页
Chinese Journal of Cardiovascular Research
关键词
苯那普利
后处理
再灌注损伤
心肌
Benazepril
Postconditioning
Reperfusion injury
Myocardium