Improvement effect and mechanism of verbascoside on arteriosclerosis of ApoE-/-mice
10.3969/j.issn.1000-484X.2025.01.018
- VernacularTitle:毛蕊花糖苷对ApoE-/-小鼠动脉粥样硬化的改善作用及机制探究
- Author:
Tao ZHANG
1
;
Zhiwei MAO
1
;
Qianyun DOU
1
;
Chenxu QIAN
1
Author Information
1. 郑州大学附属郑州中心医院心血管内科,郑州 450000
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
Verbascoside;
HMGB1/RAGE/NF-κB pathway;
Inflammation;
Endothelial cell
- From:
Chinese Journal of Immunology
2025;41(1):122-128
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of verbascoside(VERB)on high-fat diet-induced atherosclerosis(AS)in ApoE-/-mice and the effect on high mobility histone 1(HMGB1)/receptor for glycation end products(RAGE)/nuclear factor κB(NF-κB)pathway.Methods:A total of 90 ApoE-/-mice were randomly divided into normal group,AS group,VERB group,simvastatin group and VERB+pathway activator HMGB1 group,with 18 mice per group.After 8 weeks of group administration,blood and aorta samples were taken.Fasting serum triacylglycerol(TG),total cholesterol(TC)and low density lipoprotein(LDL)levels were deter-mined by automatic biochemical analyzer.Oil red O,HE and TUNEL staining were performed to observe apoptosis of aortic plaque and endothelial cell(EC).Flow cytometry was performed to analyze circulating EC numbers.Immunohistochemistry was performed to analyze the infiltration area of macrophages(CD68+)and T lymphocytes(CD3+)in aortic plaques.Western blot was performed to detect expressions of HMGB1/RAGE/NF-κB pathway,inflammation and adhesion molecules.Results:Compared with normal group,AS group had lipid plaques in arterial intima,thickness of the media was uneven,TG,TC,LDL levels,lession proportion,plaque area,circulating EC number,arterial EC apoptosis rate,macrophage(CD68+)and T lymphocyte(CD3+)infiltration areas,TNF-α,monocyte chemoattractant protein-1(MCP-1),vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),cytoplasm HMGB1,total HMGB1,total RAGE protein levels and nuclear/total p65 NF-κB levels were increased(P<0.05),while nuclear HMGB1 protein,nuclear/total HMGB1 and cytosolic p65 NF-κB levels were decreased(P<0.05).After VERB or simvastatin intervention,arterial lesions were alleviated,TG,TC,LDL levels,lession proportion,plaque area,circulating EC number,arterial EC apoptosis rate,macrophage(CD68+)and T lymphocyte(CD3+)infiltration areas,TNF-α,MCP-1,VCAM-1,ICAM-1,cytoplasm HMGB1,total HMGB1,RAGE protein levels and nuclear/total p65 NF-κB level were decreased(P<0.05),while nuclear HMGB1 protein,nuclear/total HMGB1 and cytosolic p65 NF-κB levels were increased(P<0.05),and HMGB1 was able to antagonize the protective effect of VERB on AS mice.Conclusion:VERB can inhibit expressions of inflammatory and adhesion fac-tors in arterial plaques in ApoE-/-mice,reduce EC shedding and apoptosis,therefore improve AS symptoms in ApoE-/-mice,and the mechanism may be related to the inhibition of HMGB1/RAGE and NF-κB pathway.
