| 洋蓟素对脓毒症心肌损伤小鼠的保护作用及机制 |
| 投稿时间：2025-03-19 修订日期：2025-04-02 点此下载全文 |
| 引用本文：王咪,朱小龙,吴敬医,韩保松,张霞.洋蓟素对脓毒症心肌损伤小鼠的保护作用及机制[J].医学研究杂志,2025,54(8):121-128 |
| DOI：
10.11969/j.issn.1673-548X.2025.08.020 |
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| 基金项目:安徽省高校自然科学研究重点项目(KJ2020A0616)；安徽省教育厅新时代育人质量工程项目(研究生教育2022zyxwjxalk155)；芜湖市科技计划项目(2020ms3-5)；皖南医学院教学质量与教学改革工程项目(2021ylkc17) |
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| 中文摘要:目的 探究洋蓟素对脓毒症心肌损伤的影响及潜在机制。方法 将78只雄性C57BL/6小鼠依据随机数字表法分为对照组、模型组、治疗组,每组各26只。治疗组小鼠连续7天腹腔注射洋蓟素[25mg/(kg·d)],对照组和模型组连续7天腹腔注射等量0.9%氯化钠溶液,第7天腹腔注射洋蓟素1h后,模型组和治疗组小鼠腹腔注射脂多糖(lipopolysaccharide,LPS,10mg/kg)以构建脓毒症心肌损伤模型。12h后每组随机取6只小鼠检测心功能,记录其余小鼠7天生存率。采用苏木精-伊红染色观察小鼠心肌组织结构；酶联免疫吸附试验检测炎性细胞因子、心肌损伤标志物、心肌氧化应激标志物水平；比色法检测组织铁含量；实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)法检测心肌炎性细胞因子mRNA水平；末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)染色检测心肌细胞凋亡情况；二氢乙锭(dihydroethidium,DHE)染色检测活性氧水平；Western blot法检测B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、Bcl-2-associated X的蛋白质(Bcl-2-associated X,Bax)、谷胱甘肽过氧化酶4(glutathione peroxidase 4,GPX4)、溶质载体家族7成员11(recombinant solute carrier family 7, member 11,SLC7A11)、铁蛋白重链1(ferritin heavy chain 1,FTH1)、转铁蛋白受体(transferrin receptor,TFR)、kelch样ECH相关蛋白1(kelch-like ECH associated protein 1,Keap1)、核因子-红细胞2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)的蛋白表达水平。结果 与对照组比较,模型组左心室射血分数和短轴缩短率降低,乳酸脱氢酶、肌酸激酶同工酶升高,炎性细胞因子的含量及mRNA表达水平均升高,生存率下降,心肌病理损伤显著且凋亡细胞增多,氧化应激增强,心肌GPX4、SLC7A11、FTH1、Nrf2表达抑制,TFR、Keap1表达上调,铁含量增加(P<0.05)；与模型组比较,治疗组小鼠生存率提高,心功能障碍和心肌损伤显著改善,炎性损伤、凋亡和氧化应激均减轻,同时GPX4、SLC7A11、FTH1、Nrf2表达上调,TFR、Keap1表达抑制,铁含量降低(P<0.05)。结论 洋蓟素可能通过抑制Keap1/Nrf2介导的铁死亡减轻炎症、凋亡和氧化应激,保护脓毒症心肌损伤。 |
| 中文关键词:脓毒症心肌损伤 洋蓟素 Keapl/Nrf2 铁死亡 |
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| Protective Effect and Mechanism of Cynarin on Septic Cardiomyopathy in Mice. |
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| Abstract:Objective To explore the effect and potential mechanisms of cynarin on septic cardiomyopathy. Methods Seventy-eight male C57BL/6mice were divided into three groups using a random number table method:control group, model group, and treatment group, with 26mice in each group. The treatment group received daily intraperitoneal injections of cynarin at a dose of 25mg/(kg·d) for 7days, while control group and model group received daily intraperitoneal injections with the same amount of saline. One hour after the intraperitoneal injection of cynarin on the 7th day, the model group and treatment group were intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 10mg/kg to induce septic cardiomyopathy. 12hours later, 6mice were randomly selected from each group to test cardiac function, and the remaining mice were monitored for 7-day survival. Hematoxylin-eosin staining was used to observe the histological structure of mouse myocardium; Enzyme linked immunosorbent assay were used to detect the levels of inflammatory factors, markers of myocardial injury, markers of myocardial oxidative stress; determination of tissue iron content by the colourimetric method; real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA levels of myocardial inflammatory factors; Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling(TUNEL) staining was used to detect the apoptosis of cardiac myocytes; Dihydroethidium (DHE) staining was used to detect the levels of reactive oxygen species; and Western blot was used to detect the protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X (Bax), glutathione peroxidase 4 (GPX4), recombinant solute carrier family 7, member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), transferrin receptor (TFR), kelch-like ECH associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels. ResultsCompared with the control group, mice in the model group had lower left ventricular ejection fraction and short-axis shortening rate, higher lactate dehydrogenase and creatine kinase-MB, higher content and mRNA expression of inflammatory factors, decreased survival, significant myocardial pathological damage and increased apoptotic cells, enhanced oxidative stress, inhibition of myocardial GPX4, SLC7A11, FTH1 and Nrf2 expression, and up-regulation of TFR, Keap1 expression, and increased iron content (P<0.05); Compared with the model group, mice in the treatment group had increased survival rate, significantly improved cardiac dysfunction and myocardial injury, and reduced inflammatory injury, apoptosis and oxidative stress, as well as up-regulated expression of GPX4, SLC7A11, FTH1 and Nrf2, suppressed expression of TFR and Keap1, and decreased iron content (P<0.05). Conclusion Cynarin may alleviate inflammation, apoptosis and oxidative stress by inhibiting Keap1/Nrf2-mediated ferroptosis, and protect septic cardiomyopathy. |
| keywords:Septic cardiomyopathy Cynarin Keapl/Nrf2 Ferroptosis |
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