桃叶珊瑚苷对冠心病大鼠Nrf2介导的铁死亡途径的影响  

Effects of Aucubin on Nrf2-mediated Ferroptosis Pathway in Rats with Coronary Heart Disease

作　　者：寇进 曾宪飞 原平利[1] 任锋 王颖 夏鸣扬 胡建库[1] KOU Jin;ZENG Xian-fei;YUAN Ping-li;REN Feng;WANG Ying;XIA Ming-yang;HU Jian-ku(Department of Cardiology,Shaanxi Provincial Corps Hospital,Chinese People's Armed Police Force,Xi'an,Shaanxi,710054,China;Greater Xi'an Area Medical Diagnostic Lab Center,Xi'an,Shaanxi,710016,China)

机构地区：[1]武警陕西总队医院心内科,陕西西安710054 [2]西安区域医学检验中心有限公司,陕西西安710016

出　　处：《现代生物医学进展》2024年第12期2220-2227,共8页Progress in Modern Biomedicine

基　　金：西安市科技计划-重大应用示范项目(22YYCJ-QCY3-0004)。

摘　　要：目的:探讨桃叶珊瑚苷(AU)对冠心病(CHD)大鼠的治疗作用及其对核因子红系2相关因子2(Nrf2)介导的铁死亡途径的影响。方法:将大鼠分为NC组、CHD组、L-AU组、M-AU组、H-AU组和ML385组,每组12只大鼠。NC组为正常饲料喂养的对照大鼠,其他组均为高脂饮食联合腹腔注射垂体后叶素诱导的CHD模型大鼠。NC组和CHD组大鼠灌胃0.3%羧甲基纤维素钠(CMC),L-AU组、M-AU组和H-AU组大鼠灌胃20、40和80 mg/kg/d的桃叶珊瑚苷,ML385组大鼠灌胃80 mg/kg/d的桃叶珊瑚苷并腹腔注射30 mg/kg/d Nrf2抑制剂ML385,共给药4周。分别检测各组大鼠的心功能指标[射血分数(EF)和短轴缩短率(FS)]、血清指标[肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和游离脂肪酸(FFA)]、心肌组织氧化应激指标[还原型谷胱甘肽(GSH)和丙二醛(MDA)]和心肌组织Fe^(2+)含量。通过苏木素伊红(HE)染色观察大鼠心肌形态。通过Western blot检测大鼠心肌组织中Nrf2、Kelch样ECH相关蛋白1(Keap1)、血红素加氧酶-1(HO-1)、NADPH:醌氧化还原酶-1(NQO-1)、谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)和膜铁转运蛋白1(FPN1)的蛋白水平。结果:与NC组比较,CHD组大鼠的EF和FS水平降低,CK-MB和LDH水平升高,心肌出现明显损伤;TC、TG、LDL-C、FFA和MDA水平升高,HDL-C和GSH水平降低;Nrf2、HO-1、NQO-1、GPX4、FTH1和FPN1蛋白水平降低,Keap1蛋白水平升高,Fe^(2+)含量升高(P<0.05)。与CHD组比较,L-AU组、M-AU组和H-AU组大鼠的EF和FS升高,CK-MB和LDH水平降低,心肌形态明显改善;TC、TG、LDL-C、FFA和MDA水平降低,HDL-C和GSH水平升高;Nrf2、HO-1、NQO-1、GPX4、FTH1和FPN1蛋白水平升高,Keap1蛋白水平降低,Fe^(2+)含量降低(P<0.05)。与H-AU组比较,ML385组大鼠的EF和FS降低,CK-MB和LDH水平升高,心肌损伤加重,TC、TG、LDL-C、FFA和MDA水平升高,HDL-C和GSHObjective:To explore the therapeutic effect of aucubin(AU)on rats with coronary heart disease(CHD)and its effect on the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2(Nrf2).Methods:Rats were divided into NC group,CHD group,L-AU group,M-AU group,H-AU group and ML385 group(n=12).The NC group was control rats fed with normal diet,and the other groups were rats with coronary heart disease induced by high-fat diet combined with intraperitoneal injection of pituitaryin.Rats in the NC group and CHD group were orally administered 0.3%sodium carboxymethylcellulose(CMC),and rats in the L-AU group,M-AU group,and H-AU group were orally administered 20,40,and 80 mg/kg/d of aucubin.Rats in H-AU group were orally administered 80 mg/kg/d aucubin and intraperitoneally injected with 30 mg/kg/d Nrf2 inhibitor ML385.Administration was given for a total of 4 weeks.The cardiac function indexes[ejection fraction(EF)and fractional shortening(FS)],serum indexes[creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and free fatty acids(FFA)],myocardial tissue oxidative stress indicators[glutathione(GSH)and malondialdehyde(MDA)]and Fe^(2+)content in myocardial tissue of rats in each group were measured respectively.Myocardial morphology was observed by hematoxylin-eosin(HE)staining.The protein expression levels of Nrf2,Kelch-like ECH-associated protein 1(Keap1),heme oxygenase-1(HO-1),NADPH:quinone oxidoreductase-1(NQO-1),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and membrane iron transporter 1(FPN1)in myocardial tissue were detected by Western blot.Results:Compared with NCgroup,EF and FS decreased,CK-MB and LDH levels increased,myocardial injury appeared,TC,TG,LDL-C,FFA and MDA levels increased,HDL-C and GSH level decreased,Nrf2,HO-1,NQO-1,GPX4,FTH1 and FPN1 protein expression decreased,Keap1 protein expressionincreased,Fe^(2+)content increased in CHD group(P<0.

关 键 词：桃叶珊瑚苷 冠心病 氧化应激 核因子红系2相关因子2 铁死亡 

分 类 号：R-33[医药卫生] R541.4