摘要
目的 研究桃叶珊瑚苷(AU)对阿霉素(DOX)诱导的小鼠心肌损伤的保护作用及相关分子机制.方法 40只ICR雄性小鼠随机分为对照组、DOX组、DOX+AU组和DOX+AU+ML385组.通过腹腔注射DOX建立心肌损伤模型,灌胃给予AU进行治疗,腹腔注射ML385抑制小鼠体内核因子-红细胞2相关因子2(Nrf2)的激活.治疗4周后,比较四组小鼠体重、心脏质量、心脏指数、血清心肌酶、血清氧化应激指标、心肌病理改变以及Nrf2/HO-1通路关键蛋白表达水平.结果 四组小鼠进行上述指标比较,差异均具有统计学意义(P＜0.05).DOX组小鼠体重、心脏质量、心脏指数以及血清过氧化物歧化酶(SOD)和谷胱甘肽(GSH)均显著低于对照组(P＜0.05),而血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、谷草转氨酶(AST)、丙二醛(MDA)以及心肌组织Nrf2、Keap1和HO-1蛋白表达水平均显著高于对照组(P＜0.05).DOX+AU组小鼠体重、心脏质量、心脏指数、SOD、GSH以及心肌组织Nrf2、Keap1和下游血红素氧化酶1(HO-1)蛋白表达水平均显著高于DOX组(P＜0.05),而血清LDH、CK、AST和MDA均显著低于DOX组(P＜0.05).DOX+AU+ML385组小鼠体重、心脏质量、心脏指数、SOD、GSH以及心肌组织Nrf2、Keap1和HO-1蛋白表达水平均显著低于DOX+AU组(P＜0.05),而血清LDH、CK、AST和MDA均显著高于DOX组(P＜0.05).结论 桃叶珊瑚苷对阿霉素诱导的小鼠心肌损伤具有保护作用,其机制可能与桃叶珊瑚苷激活Nrf2/HO-1通路而降低氧化应激损伤有关.
Abstract
Objective To study the protective effect and relative molecular mechanism of Aucubin(AU)on myocardial damage induced by doxorubicin(DOX)in mice.Methods Male ICR mice(n=40)were randomly divided into control group,DOX group,DOX+AU group and DOX+AU+ML385 group.The model of myocardial damage was established by intraperitoneal injection of DOX,then was intragastrically given AU for treatment and intraperitoneal injection of ML385 for inhibiting Nrf2 activation in mice.After treatment for 4 weeks,body weight,cardiac mass,cardiac index(CI),serum myocardial enzymes,serum oxidative stress indexes,myocardial pathological changes and expressions of key proteins in pathway of nuclear factor erythropoietin 2 related factor 2(Nrf2)/heme oxygenase 1(HO-1)were compared among 4 groups.Results The comparison in above-mentioned indexes had significant statistical differences among 4 groups(P<0.05).The body weight,cardiac mass,CI,superoxide dismutase(SOD)and glutathione(GSH)were significantly lower(P<0.05),and lactic dehydrogenase(LDH),creatine kinase(CK),aspertate aminotransferase(AST),malondialdehyde(MDA)and expressions of Nrf2,Keap1 and HO-1 were significantly higher(P<0.05)in DOX group than those in control group.The body weight,cardiac mass,CI,SOD,GSH and expressions of Nrf2,Keap1 and HO-1 were significantly higher(P<0.05),and LDH,CK,AST and MDA were significantly lower(P<0.05)in DOX+AU group than those in DOX group.The body weight,cardiac mass,CI,SOD,GSH and expressions of Nrf2,Keap1 and HO-1 were significantly lower(P<0.05),and LDH,CK,AST and MDA were significantly higher(P<0.05)in DOX+AU+ML385 group than those in DOX+AU group.Conclusion AU has a protective effect of myocardial damage induced by DOX in mice,and the mechanism may be related to than AU can activate Nrf2/HO-1 pathway and reduce oxidative stress damage.
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维普
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