芪冬颐心口服液激活Nrf2/HO-1信号通路减轻阿霉素诱导的小鼠心肌损伤

Qidong Yixin Oral Liquid Activates Nrf2/HO-1 Signaling Pathway to Alleviate Adriamycin-induced Myocardial Injury in Mice

目的:研究芪冬颐心口服液对阿霉素(DOX)诱导的小鼠心肌毒性保护作用及机制。方法:90只雄性ICR小鼠随机分为正常组,模型(DOX)组,DOX+芪冬颐心口服液组(9.55,23.88,47.75 g·kg^-1)及芪冬颐心口服液高剂量组(47.75 g·kg^-1),每组15只。正常组、模型组灌胃给予纯净水,芪冬颐心口服液组各剂量组灌胃给予不同剂量的芪冬颐心口服液,每天1次,给药21 d,在第7天正常组及芪冬颐心口服液高剂量组腹腔注射生理盐水,其余各组均腹腔注射阿霉素(15 mg·kg^-1)。21 d后小鼠称量体质量和心重,计算心脏指数;取血清用于乳酸脱氢酶(LDH),肌酸激酶(CK),天门冬氨酸氨基转移酶(AST)检测;取心脏用于苏木素-伊红(HE)染色;检测心肌组织内超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-PX),过氧化氢酶(CAT)活性,采用蛋白免疫印迹法(Western blot)检测核转录因子NF-E2相关因子(Nrf2),血红素氧合酶-1(HO-1)的表达。结果:与正常组比较,阿霉素可引起小鼠体质量显著降低(P<0.01),血清LDH,CK,AST活性显著升高(P<0.01),抗氧化酶活力降低(P<0.01);与DOX组比较,芪冬颐心口服液中、高剂量预给药可以显著提高小鼠体质量(P<0.05,P<0.01),降低心肌三酶水平(P<0.01),提高抗氧化酶活力(P<0.05,P<0.01),提高Nrf2及HO-1表达水平(P<0.01)。结论:芪冬颐心口服液对阿霉素心肌毒性具有很好的保护作用,其作用机制可能与激活Nrf2/HO-1信号通路,减轻氧化应激损伤有关。

Objective:To study the protective effect and mechanism of Qidong Yixin oral liquid on doxorubicin-induced myocardial toxicity in mice.Method:Ninety male ICR mice were randomly divided into normal group,model(DOX)group,DOX+Qidong Yixin oral liquid group(9.55,23.88,47.75 g·kg^-1)and high dose group(47.75 g·kg^-1)with 15 mice in each group.The normal group and model group were given pure water by gavage,and each dose group of Qidong Yixin oral liquid was given different doses of Qidong Yixin oral liquid once a day for 21 days.On the seventh day,normal saline was injected into the abdominal cavity of the normal group and the high dose group of Qidong Yixin oral liquid.Doxorubicin was injected into the abdominal cavity of the other groups(15 mg·kg^-1).After 21 days,the weight and heart weight of mice were weighed and cardiac index was calculated.Serum was taken for the detection of lactate dehydrogenase(LDH),creatine kinase(CK),aspartate aminotransferase(AST).Heart was taken for hematoxylin-eosin(HE)staining,superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),catalase(CAT)in myocardial tissue were detected.The expression of nuclear factor NF-E2 related factor(Nrf2)and heme oxygenase-1(HO-1)were detected by Western blot.Result:Compared with normal group,adriamycin could significantly reduce the body weight of mice(P<0.01),increase the activities of LDH,CK and AST in serum(P<0.01),and decrease the activities of antioxidant enzymes(P<0.01).Compared with DOX group,high dose Qidong Yixin oral liquid could significantly increase the weight of mice(P<0.05,P<0.01),decrease the level of myocardial three enzymes(P<0.01),increase the activity of antioxidant enzymes(P<0.05,P<0.01),and increase the expression of Nrf2 and HO-1(P<0.01).Conclusion:Qidong Yixin oral liquid has a good protective effect on doxorubicin myocardial toxicity.Its mechanism may be related to activating Nrf2/HO-1 signaling pathway and alleviating oxidative stress injury.