罗格列酮对兔心肌缺血再灌注损伤保护机制的研究

目的通过研究过氧化物酶体增殖物激活受体y（PPAR-γ）激动剂对心肌缺血-再灌注损伤兔模型梗死面积及组织病理学改变的影响，探讨PPAR-γ介导心脏保护作用的可能机制。方法新西兰白兔40只随机分为5组，包括：假手术组、模型组、罗格列酮低剂量组、罗格列酮高剂量组及罗格列酮高剂量＋GW9622组。假手术组只开胸穿线不结扎心脏，其余组兔冠状动脉左前降支结扎30min，再灌注120min。建立心肌缺血再灌注模型后1h分别检测血清一氧化氮（NO）、超氧化物歧化酶（T-SOD）浓度；ELISA法检测血清炎症因子白介素-6（IL-6）浓度；术后取兔心脏，硝基四氮唑蓝（NBT）染色后评价心肌梗死面积；做HE染色切片及电镜片观察组织及超微结构改变。结果与模型组和罗格列酮高剂量＋GW9622组相比，罗格列酮低剂量组、罗格列酮高剂量组血清NO含量降低，IL-6浓度显著降低，血清T-SOD浓度显著升高（P〈0．01）；心肌梗死面积明显下降，心肌病理结构改变较轻，心肌细胞超微结构损坏破坏程度也明显减轻。结论罗格列酮通过提高血清T-SOD水平减轻氧化应激，抑制炎症因子IL-6的生成减轻炎症反应，起到减轻心肌损伤，降低心肌梗死面积的保护作用。

Study on the Protective Mechanisms of Rosiglitazone on Myocardial Ischemia Reperfusion Injury in Rabbits

OBJECTIVE To explore the mechanisms and protective effect ofperoxisome proliferators-activated receptor-γ （PPAR-γ） agonist on myocardial ischemia reperfusion（I/R） injury rabbits by observation the size of myocardial infarction and thehistopathological changes. METHODS Forty New Zealand white rabbits were randomly divided into five groups（n-8）： sham group, model group, low dose of rosiglitazone group, high dose of rosiglitazone group and high dose of rosiglitazone＋GW9622 group. Thoracotomy and threading of the coronary artery without ligation was performed in sham group, whereas the coronary artery was ligated for 30 min, under 120 min reperfusion in othe groups. Plasma concentration of NO, T-SOD and serum inflammatory cytokines IL-6 were tested after 1 h of I/R. The heart were harvested after I/R for pathological and ultrastructure analysis, and the areas of myocardial infarction were assessed. RESULTS Compared with model group and high dose of rosiglitazone＋GW9622 group, in low dose of rosiglitazone group and high dose of rosiglitazon group, the plasma concentration of NO and IL-6 decreased, T-SOD significantly increased; the size of myocardial infarct decreased, and myocardial pathological and ultrastructure changes significantly improved. CONCLUSION The results indicate that PPAR-）, agonist of rosiglitazone can attenuate myocardial ischemia reperfusion injury, improve myocardial pathological and ultrastructure, reduce infarct size by mitigating oxidative stress and reducing the inflammatory response.