Protective Effect and Mechanism of Cynarin on Septic Cardiomyopathy in Mice
10.11969/j.issn.1673-548X.2025.08.020
- VernacularTitle:洋蓟素对脓毒症心肌损伤小鼠的保护作用及机制
- Author:
Mi WANG
1
;
Xiaolong ZHU
1
;
Jingyi WU
1
Author Information
1. 241004 芜湖,皖南医学院第一附属医院
- Publication Type:Journal Article
- Keywords:
Septic cardiomyopathy;
Cynarin;
Keapl/Nrf2;
Ferroptosis
- From:
Journal of Medical Research
2025;54(8):121-128
- CountryChina
- Language:Chinese
-
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 25 mg/(kg·d)for 7days,while control group and model group received daily intraperitoneal injections with the same amount of saline.One hour after the in-traperitoneal injection of cynarin on the 7th day,the model group and treatment group were intraperitoneally injected with lipopolysaccha-ride(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 histo-logical structure of mouse myocardium;Enzyme linked immunosorbent assay were used to detect the levels of inflammatory factors,mark-ers 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.Results Compared 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 inflam-mation,apoptosis and oxidative stress by inhibiting Keap1/Nrf2-mediated ferroptosis,and protect septic cardiomyopathy.
