注射用苦碟子对大鼠心肌缺血再灌注损伤的保护作用及其机制

Protective effect of Kudiezi for injection on myocardial ischemia-reperfusion injury in rats and its mechanism

目的研究注射用苦碟子(KDZI)对大鼠心肌缺血再灌注损伤的保护作用及其机制。方法通过大鼠在体结扎冠状动脉前降支30 min后,松扎再灌注120 min制备心肌缺血再灌注损伤模型,计算心肌梗死范围(MIS),测定血清天门冬氨酸氨基转换酶(AST)、磷酸肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量,血浆内皮素(ET)、血管紧张素Ⅱ(AngⅡ)、前列环素(PGI2)及血栓素A2(TXA2)水平。同时测心肌梗死及非梗死区游离脂肪酸(FFA)含量。结果KDZI对心肌缺血30 min再灌注损伤120 min大鼠,可明显缩小MIS,降低血清AST、CK、LDH活性及MDA含量,提高SOD及GSH-Px活性,能使血浆ET、AngⅡ及TXA2水平明显下降,PGI2水平及PGI2/TXA2比值明显增高,亦可使心肌梗死及非梗死区FFA含量明显降低。结论KDZI对大鼠心肌缺血再灌注损伤具有明显保护作用,可能与其增强抗氧化酶活性,减少自由基对心肌的氧化损伤,纠正心肌缺血时FFA代谢紊乱,减少内源性血管活性物质ET及AngⅡ释放,纠正PGI2/TXA2失衡等机制有关。

Objective To investigate protective effect of Kudiezi for injection(KDZI) on myocardial ischemia-reperfusion injury in rats and its mechanism.Methods The myocardial ischemia-reperfusion model was induced by left anterior descending coronary occulusion in 30 min and reperfusion in 120 min in rats.The changes of myocardial infarct size(MIS),serum aspartate aminotransferase(AST),creatine phosphokinase(CK) and lactate dehydrogenase(LDH) activity,malondialdehyde(MDA) content,superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) activity,and plasma endothelin(ET),angiotensinⅡ(AngⅡ),prostacycline(PGI2),thromboxane A2(TXA2) levels,and myocardial free fatty acid(FFA) content of infarct and noninfarct area were determined.Results In rats treated by KDZI(in a dosage of 2.5,5 and 10mg.kg-1 i.v ),the MIS was significantly reduced,the serum AST,CK and LDH activity,the plasma ET,AngⅡ and TXA2 level and myocardial FFA content declined,while plasma PGI2 level and PGI2/TXA2 was increased signficatly.In addition,serum MDA content declined,SOD and GSH-Px activity were increased markedly.Conclusion KDZI is of protective effect on myocardial ischemia-reperfusion injury in rats by improving free radicals and myocardial metabolism,decreasing plasma ET,AngⅡ and TXA2 levels and increasing plasma PGI2 level and PGI2/TXA2 ratio etc.