Berberine Inhibits Ferroptosis and Stabilizes Atherosclerotic Plaque through NRF2/SLC7A11/GPX4 Pathway  

作　　者：WANG Ting-ting YU Li-li ZHENG Jun-meng HAN Xin-yi JIN Bo-yuan HUA Cheng-jun CHEN Yu-shan SHANG Sha-sha LIANG Ya-zhou WANG Jian-ru 

机构地区：[1]Heart Center,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,450000,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第10期906-916,共11页中国结合医学杂志（英文版）

基　　金：Supported by the Henan Province Science and Technology Research Project(No.182102310093)。

摘　　要：Objective:To investigate potential mechanisms of anti-atherosclerosis by berberine(BBR)using ApoE-/-mice.Methods:Eight 8-week-old C57BL/6J mice were used as a blank control group(normal),and 568-week-old AopE-/-mice were fed a high-fat diet for 12 weeks,according to a completely random method,and were divided into the model group,BBR low-dose group(50 mg/kg,BBRL),BBR medium-dose group(100 mg/kg,BBRM),BBR high-dose group(150 mg/kg,BBRH),BBR+nuclear factor erythroid 2-related factor 2(NRF2)inhibitor group(100 mg/kg BBR+30 mg/kg ML385,BBRM+ML385),NRF2 inhibitor group(30 mg/kg,ML385),and positive control group(2.5 mg/kg,atorvastatin),8 in each group.After 4 weeks of intragastric administration,samples were collected and serum,aorta,heart and liver tissues were isolated.Biochemical kits were used to detect serum lipid content and the expression levels of malondialdehyde(MDA)and superoxide dismutase(SOD)in all experimental groups.The pathological changes of atherosclerosis(AS)were observed by aorta gross Oil Red O,aortic sinus hematoxylin-eosin(HE)and Masson staining.Liver lipopathy was observed in mice by HE staining.The morphology of mitochondria in aorta cells was observed under transmission electron microscope.Flow cytometry was used to detect reactive oxygen species(ROS)expression in aorta of mice in each group.The content of ferrous ion Fe^(2+)in serum of mice was detected by biochemical kit.The mRNA and protein relative expression levels of NRF2,glutathione peroxidase 4(GPX4)and recombinant solute carrier family 7 member 11(SLC7A11)were detected by quantitative real time polymerase chain reaction(RT-q PCR)and Western blot,respectively.Results:BBRM and BBRH groups delayed the progression of AS and reduced the plaque area(P<0.01).The characteristic morphological changes of ferroptosis were rarely observed in BBR-treated AS mice,and the content of Fe^(2+)in BBR group was significantly lower than that in the model group(P<0.01).BBR decreased ROS and MDA levels in mouse aorta,increased SOD activity(P<0.01),significan

关 键 词：BERBERINE ApoE−/− ferroptosis ATHEROSCLEROSIS oxidative stress NRF2/SLC7A11/GPX4 pathway 

分 类 号：R285.5[医药卫生—中药学]