南方医科大学学报2025,Vol.45Issue(9):1818-1829,12.DOI:10.12122/j.issn.1673-4254.2025.09.02
"气经-血络"截断动脉粥样硬化斑块形成:降脂化斑方调控小鼠肝脏逆向胆固醇转运途径改善动脉粥样硬化的机制
Disrupting atherosclerotic plaque formation via the"qi meridian-blood channel":mechanism of Jiangzhi Huaban Decoction for regulating hepatic reverse cholesterol transport to improve atherosclerosis
摘要
Abstract
Objective To explore the molecular mechanism of Jiangzhi Huaban Decoction(JZHBD)for improving atherosclerosis through the"qi meridian-blood channels"pathway.Methods ApoE-/-mouse models of atherosclerosis were established by high-fat diet feeding for 8 weeks,with C57BL/6 mice on a normal diet as the controls.Forty ApoE-/-mouse models were randomized into model group,low-,medium-,and high-dose JZHBD treatment groups,and atorvastatin treatment group(n=8)for their respective treatments for 8 weeks.The changes in body weight and overall condition of the mice were monitored weekly.After the treatments,serum levels of TC,TG,HDL-C,LDL-C,TBA,ALT,and AST of the mice were measured,pathological changes in the liver and aortic root plaques were examined with HE staining,and lipid accumulation in the liver and aortic wall was assessed using Oil Red O staining.The core molecular mechanism was studied through transcriptomics,and the expressions of the key pathway proteins were confirmed using Western blotting and immunohistochemistry.Results Treatment with JZHBD significantly reduced blood lipid and total bile acid levels,improved liver function and hepatic steatosis,and decreased aortic lipid deposition and plaque area in the mouse models of atherosclerosis.Transcriptomic analysis suggested that the therapeutic mechanism of JZHBD involved reverse cholesterol transport,PPAR signaling,and the inflammatory pathways.In atherosclerotic mice,JZHBD treatment obviously up-regulated hepatic expressions of PPARγ,LXRα,ABCA1,ABCG1,and CYP7A1,down-regulated hepatic expressions of p-p65/p65,IL-6,IL1β in the liver,increased ABCG5 and ABCG8 expressions in the intestines,and decreased ICAM-1 and VCAM-1 expressions in the aortic plaques.Conclusion JZHBD improves atherosclerotic vascular damage and plaque formation possibly by regulating hepatic reverse cholesterol transport and inflammation via modulating the hepatic PPARγ/LXRα/NF-κB signaling pathway.关键词
动脉粥样硬化/气经-血络/降脂化斑方/胆固醇逆向转运/血管细胞黏附分子Key words
atherosclerosis/qi meridian-blood channels/Jiangzhi Huaban Decoction/reverse cholesterol transport/vascular cell adhesion molecules引用本文复制引用
王宏杨,朱文怡,陈栩燊,张童,曹志伟,王金,解渤,刘强,任雪峰.."气经-血络"截断动脉粥样硬化斑块形成:降脂化斑方调控小鼠肝脏逆向胆固醇转运途径改善动脉粥样硬化的机制[J].南方医科大学学报,2025,45(9):1818-1829,12.基金项目
浙江中医药大学校级科研项目(2023RCZXZK12) (2023RCZXZK12)
浙江省中医药科技计划项目(2025ZR106) (2025ZR106)