| 寇 进,曾宪飞,原平利,任 锋,王 颖,夏鸣扬,胡建库.桃叶珊瑚苷对冠心病大鼠Nrf2介导的铁死亡途径的影响[J].,2024,(12):2220-2227 |
| 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 |
| 投稿时间：2023-12-24 修订日期：2024-01-20 |
| DOI：10.13241/j.cnki.pmb.2024.12.004 |
| 中文关键词: 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 |
| 英文关键词: Aucubin Coronary heart disease Oxidative stress Nuclear factor erythroid 2-related factor 2 Ferroptosis |
| 基金项目:西安市科技计划-重大应用示范项目（22YYCJ-QCY3-0004） |
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| 中文摘要: |
| 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Fe2+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，Fe2+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，Fe2+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，Fe2+含量升高（P<0.05）。结论：桃叶珊瑚苷表现出了良好的抗冠心病作用，其机制与抑制Nrf2介导的铁死亡途径有关。 |
| 英文摘要: |
| ABSTRACT Objective: 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 Fe2+ 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 NC group, 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 expression increased, Fe2+ content increased in CHD group (P<0.05). Compared with CHD group, EF and FS increased, CK-MB and LDH levels decreased, myocardial morphology was significantly improved, TC, TG, LDL-C, FFA and MDA levels decreased, HDL-C and GSH level increased, Nrf2, HO-1, NQO-1, GPX4, FTH1 and FPN1 protein expression increased, Keap1 protein expression decreased and Fe2+ content decreased in L-AU group, M-AU group and H-AU group (P<0.05). Compared with H-AU group, EF and FS decreased, CK-MB and LDH increased, myocardial injury aggravated, TC, TG, LDL-C, FFA and MDA increased, HDL-C and GSH decreased, Nrf2, HO-1, NQO-1, GPX4, FTH1 and FPN1 protein expression decreased, Keap1 protein expression increased, Fe2+ content increased in ML385 group (P<0.05). Conclusion: Auucrin shows good anti-coronary heart disease effect, and its mechanism is related to inhibiting the Nrf2-mediated ferroptosis pathway. |
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