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在心肌缺血/再灌注(MI/R)时,一氧化氮(NO)生成量减少,氧自由基(ROS)大量堆积,均可加重MI/R损伤。据此设计合成了可同时释放NO的ROS清除剂——乙酰阿魏单硝酸异山梨醇酯(AFI),并研究了AFI对MI/R大鼠的心肌保护作用及其作用机制。建立常规大鼠MI/R(30min/3h)模型,随机给予AFI(10mg·kg-1)、阿魏酸(40mg·kg-1)或单硝酸异山梨酯(30mg·kg-1)药物治疗(ig),再灌注末检测大鼠心肌梗死面积和心功能指标,同时测定血清肌酸激酶、乳酸脱氢酶、超氧化物歧化酶活性、过氧化氢与丙二醛水平及NO含量。与阿魏酸钠、单硝酸异山梨醇单独治疗组或联合治疗组相比,AFI治疗组心肌梗死面积显著减小(n=8,P<0.01),左室发展压、左室等容收缩/舒张期压力上升或下降最大速率显著提高(n=8,P<0.05),血清肌酸激酶和乳酸脱氢酶活性显著降低。与阿魏酸钠或单硝酸异山梨醇单独治疗组相比,AFI治疗组血清超氧化物歧化酶活性增加、过氧化氢与丙二醛含量降低而NO含量显著升高(n=8,P均<0.05)。这些结果表明,AFI这一新化合物可减轻大鼠MI/R损伤,具有保护心脏功能,其心肌保护作用比阿魏酸钠、单硝酸异山梨醇的单独使用或联合使用均强。
During myocardial ischemia / reperfusion (MI / R), nitric oxide (NO) production decreased and oxygen free radicals (ROS) accumulated significantly, both of which increased MI / R injury. The ROS scavenger, acetylsalicylic acid monostearate (AFI), which can release NO simultaneously, was designed and synthesized. The myocardial protective effect of AFI on MI / R rats and its mechanism were also studied. The conventional rat model of MI / R (30 min / 3 h) was established and treated with AFI (10 mg · kg -1), ferulic acid (40 mg · kg -1) or isosorbide mononitrate (30 mg · kg -1) (ig), myocardial infarct size and cardiac function were measured at the end of reperfusion. Serum creatine kinase, lactate dehydrogenase, superoxide dismutase activity, hydrogen peroxide and malondialdehyde levels and NO content were measured. Compared with sodium ferulate, isosorbide mononitrate monotherapy group or combination therapy group, AFI treatment group myocardial infarct size was significantly reduced (n = 8, P <0.01), left ventricular development pressure, left ventricular isovolumic contraction / Maximal rate of increase or decrease of diastolic pressure was significantly increased (n = 8, P <0.05), serum creatine kinase and lactate dehydrogenase activity was significantly decreased. Compared with sodium ferulate or isosorbide mono-nitrate monotherapy group, serum superoxide dismutase activity increased, hydrogen peroxide and malondialdehyde levels decreased and NO content increased significantly (n = 8, P All <0.05). These results indicate that the new AFI compound attenuates MI / R injury in rats and protects cardiac function, and its cardioprotective effect is stronger than sodium ferulate, isosorbide mononitrate alone or in combination.