橄榄苦苷对缺血再灌注大鼠心肌应激性炎症损伤的保护作用

Protective effect of oleuropein on stress-induced inflammatory injury in myocardial ischemia-reperfusion rats

目的:探索橄榄苦苷(Ole)对缺血再灌注大鼠(I/RI)心肌应激性炎症损伤的保护作用。方法:将48只SD大鼠随机分为对照组、I/RI组(结扎左冠状动脉前降支)、Ole组(40 mg/kg,连续灌胃14 d)和依达拉奉(EDA)组(阳性对照,腹腔注射6 mg/kg),12只/组。造模15 d,检测大鼠心功能、血清心肌损伤标志物、心肌组织超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)水平,ELISA检测造模第1~15天的血清TNF-α水平变化,检测心肌组织诱导型一氧化氮合酶(iNOS)和IL-10表达。分别采用H_(2)O_(2)(100μmol/L)和LPS(10μmol/L)诱导H9C2细胞损伤,采用Ole(40μg/ml)和EDA(6μg/ml)干预后,检测各组TNF-α、iNOS和IL-10蛋白表达。结果:I/RI组大鼠心功能低于对照组,心肌损伤标志物水平高于对照组,心肌组织SOD和GSH水平低于对照组,MDA、iNOS、IL-10表达高于对照组(P<0.05);Ole组和EDA组大鼠心功能高于I/RI组,血清心肌损伤标志物水平低于I/RI组,心肌组织SOD、GSH和IL-10表达高于I/RI组,MDA和iNOS表达低于I/RI组(P<0.05)。造模第9天、第12天和第15天,Ole组和EDA组血清TNF-α水平低于造模第3天(P<0.05)。H_(2)O_(2)组和LPS组心肌细胞TNF-α、iNOS、IL-10蛋白表达高于对照组(P<0.05);Ole组和EDA组心肌细胞TNF-α、iNOS蛋白表达低于H_(2)O_(2)组和LPS组,IL-10蛋白表达高于H_(2)O_(2)组和LPS组(P<0.05)。结论:Ole可降低心肌I/RI大鼠的氧化应激水平,抑制心肌组织炎症反应,减轻心肌组织损伤,改善心功能。

Objective:To explore protective effect of oleuropein(Ole)on stress induced myocardial inflammatory injury in ischemic reperfusion(I/RI)rats.Methods:Forty-eight SD rats were randomly divided into control group,I/RI group(ligation of left anterior descending coronary artery),Ole group(40 mg/kg,intragastric administration for 14 d)and edaravone(EDA)group(positive control group,intraperitoneal injection of 6 mg/kg),for 12 rats in each group.At 15 d after molding,cardiac function,levels of serum myocardial injury markers,superoxide dismutase(SOD),glutathione(GSH)and malondialdehyde(MDA)in rats were detected.At 1~15 d after molding,level of serum TNF-αwas detected by ELISA.Expression of inducible nitric oxide synthase(iNOS)and IL-10 in myocardial tissues were detected.H9C2 cell damage was induced by H_(2)O_(2)(100μmol/L)and LPS(10μmol/L)respectively.After intervention with Ole(40μg/ml)and EDA(6μg/ml),expressions of TNF-α,iNOS and IL-10 protein in each group were de⁃tected.Results:Heart function of rats in I/RI group were lower than those in control group,levels of myocardial injury markers were higher than those in control group,SOD and GSH in myocardial tissue were lower than those in control group,and expressions of MDA,iNOS and IL-10 were higher than those in control group(P<0.05).Heart function of rats in Ole and EDA groups were higher than those in I/RI group,levels of serum myocardial injury markers were lower than those in I/RI group,SOD,GSH and IL-10 in myocardial tissue were higher than those in I/RI group,and expressions of MDA and iNOS were lower than that in I/RI group(P<0.05).At 9 d,12 d and 15 d after modeling,level of serum TNF-αwere lower than that at 3 d after molding in Ole group and EDA group(P<0.05).Expressions of TNF-α,iNOS and IL-10 in H_(2)O_(2) group and LPS group were higher than those in control group(P<0.05).Expressions of TNF-αand iNOS in Ole group and EDA group were lower than that in H_(2)O_(2) group and LPS group,while IL-10 protein were higher than that in H_(2)O_(2) group and LPS group(P<0.05).Conclusion:Ole can reduce oxidative stress level of rats with myocardial I/RI,inhibit inflammation response in myocardial tissues,reduce myocardial tissue damage,and improve cardiac function.