香芹酚对大鼠心肌缺血/再灌注损伤的保护作用及相关机制

Protective effect of carvacrol on myocardial ischemia/reperfusion injury in rats and its related mechanism

目的探讨香芹酚(CAR)对大鼠心肌缺血/再灌注损伤(I/R)的保护作用及相关分子机制。方法结扎大鼠左冠状动脉前降支制作心肌缺血(30 min)/再灌注(120 min)模型,将大鼠随机分为5组:对照组(A组),模型组(B组),香芹酚10 mg/kg组(C组),香芹酚25 mg/kg组(D组),香芹酚50 mg/kg组(E组)。A组大鼠麻醉后行开胸术,分离左前降支但不结扎,B组于心肌缺血前30 min通过股静脉注入0.5 ml生理盐水,后行缺血/再灌注术,C、D、E组于缺血前30 min分别通过股静脉注入10 mg/kg、25 mg/kg和50 mg/kg香芹酚溶剂,后行缺血/再灌注术。造模后检测心肌梗死面积、ELISA法检测心肌组织氧化应激因子丙二醛(MDA)、过氧化氢酶(CAT)、过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH),Western blot法检测心肌细胞凋亡蛋白Bax及Bcl-2表达。结果造模后B组梗死面积明显大于A组(P<0.05),而香芹酚预处理后,梗死面积逐渐减小,并呈剂量依赖性(P<0.05);ELISA显示,造模后B组MDA含量明显提高(P<0.05),CAT、SOD和GSH活性明显降低(P<0.05),而香芹酚预处理后,MDA含量明显降低,CAT、SOD和GSH活性明显提高,并呈剂量依赖性(P<0.05);Western blot显示,造模后B组Bax蛋白表达显著提高(P<0.05),Bcl-2显著降低(P<0.05),而香芹酚预处理后,Bax蛋白表达显著降低(P<0.05),Bcl-2显著提高(P<0.05)。结论香芹酚能通过抑制氧化应激反应及心肌细胞凋亡保护大鼠心肌缺血/再灌注损伤。

Objective To explore the effect of carvacrol（CAR） on myocardial ischemia/reperfusion injury in rats and its related mechanism. Methods Ischemia（30 min）/reperfusion（120 min） model was made via ligation of left anterior descending coronary artery. All rats were divided into 5 groups： group A（control group）,group B（model group）,group C（CAR 10 mg/kg）,group D（CAR 25 mg/kg）,group E（CAR50 mg/kg）. Group A rats underwent thoracotomy,and the left anterior descending branch was isolated but not ligated. Group B was injected with0. 5 ml normal saline through the femoral vein 30 min before myocardial ischemia,followed by ischemia/reperfusion,C,D,Group E was injected with 10 mg/kg,25 mg/kg and 50 mg/kg carvacrol solvent through the femoral vein 30 min before ischemia,followed by ischemia/reperfusion.CAR was pretreated before the model was made,and the area of myocardial infarction was detected using triphenyl tetrazolium chloride stain. Content of malondialdehyde（MDA）,catalase（CAT）,superoxide dismutase（SOD） and glutathione peroxidase（GSH） were valued by ELISA. Meanwhile,the relative protein expression of Bax and Bcl-2 were detected by western blot. Results Myocardial infarction area in group B was significantly higher than that in group A（P〈0. 05）,while,pretreated with CAR could markedly decrease the myocardial infarction area（P〈0. 05）. Elisa showed that the content of MDA was significantly higher than group A（P〈0. 05）,and the activity of CAT,SOD and GSH were markedly lower than that of group A,while,pretreated with CAR could markedly reverse the expression of oxidative stress factors（P〈0. 05）. Western blot showed that carvacrol could significantly up-regulated the protein expression of Bcl-2 and down-regulated the Bax（P〈0. 05）. Conclusion Carvacrol can significantly protect the myocardial ischemia/reperfusion injury via its anti-oxidative stress and anti-apoptotic pathway.