目的观察Necrostatin-1(Nec-1)对大鼠慢性心肌缺血后心功能和心肌反应性纤维化的影响。方法成年雄性SD大鼠被随机分为Nec-1处理组(7例)、溶剂对照组(例)和伪手术组(5例)。通过结扎冠状动脉左前降支建立心肌缺血模型,并于结扎的同时,给予大鼠尾静脉Nec-1(0.6mg/kg)或相应溶剂对照。在缺血2周后,观察左心室功能的改变,并用Masson氏染色法观察心肌反应性纤维化后心肌反应性纤维化的程度并测定相应的心肌梗死面积。结果应用Nec-1后与溶剂对照组比较,各项心功能指标如左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、最大收缩速率(+dp/dtmax)以及最大舒张速率(-dp/dtmax)均有明显改善;心肌反应性纤维化及心梗面积也显著减少[(3.5±1.0)%比(13.2±0.5)%,P〈0.01)]。结论Nec—1可以明显地抑制慢性心肌缺血大鼠的心肌反应性纤维化并改善心功能,具有显著的心肌保护作用。
Objective To determine the protective effects of Necrostatin-1 on cardiac function and yocardial reactive fibrosis in rats subjected to chronically myocardium ischemia (MI).injury. Methods Male adult SD rats were divided randomly into 3 groups: MI plus Nec-1 group (n=7), MI plus vehicle group (n=7) and sham-operated group (n=5). Chronically myocardial ischemia was produced by deligating left anterior descending (LAD) in rats, and the administration of Necrostatin-1 (0.6 mg/kg) or vehicle via caudal vein at the onset of ischemia. After 2 weeks ischemia, cardiac function was measured to assess myocardial injury. The eventual myocardial infarction size and reactive fibrosis was confirmed by Masson's trichrome stains. Results Compared with vehicle group, the administration of Nec-1 significantly reduced myocardial reactive fibrosis and infarct size (3.5%±1.0% vs 13.2%± 0.5%,P〈0.01) and ameliorated cardiac dysfunction (LVSP, LVEDP, +dp/dtmax, -dp/dtmax) in rats subjected to chronically myocardial ischemia in vivo. Conclusion Necrostatin-1 may significantly reduce myocardial reactive fibrosis and ameliorate cardiac dysfunction, which consequently possess a cardiopretective effect in chronically myocardial ischemia.