摘要
目的:探讨白藜芦醇对心肌缺血再灌注损伤大鼠炎症和氧化应激的影响及可能的作用机制。方法:30只SD大鼠随机分为假手术组(Sham组)、缺血再灌注组(MI/R组)、白藜芦醇预处理组(MI/R+Res组),采用结扎左冠状动脉前降支起始部制作大鼠心肌缺血再灌注损伤模型,Sham组穿针后不结扎,MI/R组于缺血前15min以及再灌注前1 min舌下静脉注入10 mg/kg生理盐水,MI/R+Res组静脉注入等量白藜芦醇,对比三组心功能指标左心室舒张末期压(LVEDP)、左心室射血分数(LVEF)、左室内压力变化最大上升和下降速率(±dp/dt max),心肌梗死面积,心肌损伤标志物肌酸激酶(CK)乳酸脱氢酶(LDH),冠状动脉炎症标志物髓过氧化酶(MPO),氧化应激指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA),Western blot检测Nrf2/ARE信号通路蛋白Nrf2和HO-1蛋白表达。结果:与Sham组比较,MI/R组LVEDP、心肌梗死面积、CK、LDH、MPO、MDA显著升高,而LVEF、+dp/dt max、-dp/dt max、SOD、GSH-PX显著降低,差异有统计学意义(P<0.05);MI/R+Res组LVEDP、心肌梗死面积、CK、LDH、MPO、MDA均显著低于MI/R组,LVEF、+dp/dt max、-dp/dt max、SOD、GSH-PX均显著高于MI/R组,差异有统计学意义(P<0.05);Western blot显示Sham组Nrf2和HO-1蛋白表达较少,MI/R组Nrf2和HO-1蛋白表达显著增加,与MI/R组比较,MI/R+Res组Nrf2和HO-1蛋白表达显著增加,差异有统计学意义(P<0.05)。结论:白藜芦醇可能通过激活Nrf2/ARE信号通路降低心肌缺血再灌注损伤大鼠炎症和氧化应激。
Objective： To explore the influence of resveratrol on inflammatory response and oxidative stress in myocardial ischemia-reperfusion injury rats and the possible mechanism of action. Methods： Thirty SD rats were randomly divided into control group（ Sham group）,ischemia reperfusion group（ MI/R group） and resveratrol pretreatment group（ MI/R ＋ Res group）. The model of acute myocardium ischemia reperfusion injury was performed by occlusion of left descending coronary artery followed by reperfusion in open-chest rats. Rats in Sham group were not sealed after the needle and those in MI/R group were administered normal saline（ 10 mg/kg） 15 min before myocardial ischaemia followed by 1min before the reperftion. Rats in MI/R ＋ Res group were administered Res（ 10 mg/kg） 15 min before myocardial ischaemia followed by 1 min before the reperftion. Check the cardiac function index： left ventricular end-diastolic pressure（ LVEDP） and left ventricular ejection fraction（ LVEF）,left indoor pressure change maximum rising and falling rate（ ±dp/dt max）,myocardial infarction area,myocardial injury markers： creatine kinase（ CK）,lactate dehydrogenase（ LDH）,coronary inflammation marker： myeloperoxidase（ MPO）,oxidative stress indicators： superoxide dismutase（ SOD）,glutathione peroxidase（ GSH-PX） and malondialdehyde（ MDA）. Decet the expressions of Nrf2 and HO-1protein with Western blot. Results： Compared with the Sham group,the levels of LVEDP,myocardial infarction area,CK,LDH,MPO and MDA were increased significantly in MI/R group while the LVEF,＋ dp/dt max,-dp/dt max,SOD and GSH-PX were significantly reduced. The difference was statistically significant（ P〈0. 05）. The levels of LVEDP,myocardial infarction area,CK,LDH,MPO and MDA were significantly lower than those of the MI/R group,while the LVEF,＋ dp/dt max,-dp/dt max,SOD and GSH-PX were significantly higher than those of MI/R group. The difference was statistically significant（ P〈0. 05）. Western blot showed that the expression of Nrf2 protein in Sham group and was less and HO-1and Nrf2 protein expressions in MI/R group were increased significantly. Compared with MI/R group,the HO-1 and Nrf2 protein expressions increased significantly and the difference was statistically significant（ P〈0. 05）. Conclusion：Resveratrol can reduce the inflammatory response and oxidative stress in myocardial ischemia-reperfusion injury rats may through activating Nrf2/ARE signaling pathway.
出处
《中华中医药学刊》
CAS
北大核心
2017年第6期1516-1520,共5页
Chinese Archives of Traditional Chinese Medicine
基金
浙江省中医药科技计划项目(2013ZB045)
