非拉尼特对大鼠缺血-再灌注心肌的保护作用

Protective Effect of Ferilnite on the Myocardium Submitted to Ischemia/Reperfusion Injury in Rats

目的探讨阿魏酸硝酸酯类药物非拉尼特(FLNT)对大鼠缺血-再灌注心肌的保护作用及其机制。方法采用大鼠在体缺血-再灌注模型,将动物随机分为6组。假手术组(对冠脉只穿线不结扎);模型对照组(给予等剂量的0.5%羧甲基纤维素钠溶液);FLNT低、中、高剂量药物组(分别给予FLNT2,4,8 mg.kg-1);阳性对照组(给予硝酸甘油2 mg.kg-1)。大鼠进行缺血40 min,再灌注3 h后测定心肌梗死范围、心肌组织及血清学指标,并定时记录心电图。结果FLNT组心肌梗死面积、血清肌酸激酶和乳酸脱氢酶活性明显减少(P<0.05),心肌组织中一氧化氮(NO)含量和超氧化物歧化酶(SOD)活性显著增加,丙二醛含量显著下降(P<0.05)。能显著地阻止T波的升高(P<0.05)和R波的降低(P<0.05),降低病理性Q波的产生。结论FLNT对大鼠缺血-再灌注心肌有保护作用,其机制与NO升高以及机体的抗氧化能力增强有关。

Objective To probe into the protective effect of ferilnite（ FLNT）, a drug belonging to the class of ferulic acid nitric ester, on the myocardium submitted to ischemia./reperfusion injury in rats. Methods Sixty male adult SD rats were divided into 6 equal groups . Except for rats of the sham operation group （ group （1）） in which a thread was passed beneath the coronary artery but the vessel was not ligated, a model of ischemia/reperfusion injury of the myocardium was set up in each of the rats of the other 5 groups by ligating the left anterior descending branch of the coronary artery for 40 min followed by untying of the vessel for 3 h. 10 min after the ligation of the artery, rats of group （2）（ model group）, group （3）（4）and（5）（ FLNT treatment group） and group （6）（ positive control group ） were given each by gastragavage an equivalent amount of carboxymethylcellulose （CMC） , 2,4 and 8 mg · kg^-1 of FLNT and 2 mg·kg^- 1 of nitroglycerine, respectively. Blood samples were taken from the common carotid artery at the termination of the 3 h reperfusion and the hearts extirpated for examination. ECG was recorded 10 min before and after the ligation of the artery and at different time points after the administration of the drugs. Results The size of myocardial infarction was much smaller, the activities of serum creatine kinase （CK） and lactate dehydrogenase （LDH） were significantly lower （ P 〈 0. 05 ） , the content of nitric oxide （NO） and activity of superoxide dismutase （SOD） in the myocardial tissue were strikingly higher, while the content of malonyldialdehyde （MDA） was dramatically lower in rats treated with different doses of FLNT（ P 〈0.05 ） as compared with those parameters in rats of the model group. FLNT was also shown to prevent the elevation of T wave, depression of the R wave （ P 〈 0.05 ） and production of the pathological Q wave. Conclusion FLNT was shown to exert protective effects on the myocardium submitted to an ischemia/reperfusion injury in rats possibly by up-regulating myocardial NO and strengthening the anti-oxidative mechanism of the organism.