Abstract: Objective To investigate the beneficial effect ofberberine(BBR) on atherosclerosisin Apo-/-E mice and explore the underlying mechanisms. Methods 48 Apo-/-E mice，at 6-8 weeks old，were randomly allocated into 4 groups: Control, Model(fed with high-fat diet for 4 weeks),BBR( p.o.，100 mg/(kg?d)) and Atorvastatin (p.o., 5 mg/(kg?d))groups with 12 mice in each group.. The morphology and inflammation infiltration of aortic were examined with HE staining. The expression of BMP-2，OPG，OCN，RUNX2 in aortic was examined by immumohistochemical staining. Blood lipid levels were examined by automatic biochemical analyzer. The expression of IL-6, TNF-α and BMP-2 in serum and tissues was detected by ELISA method. The expression of ALP and the content of calcium were detected by commercially-available kits. HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24h. The contents of ICAM-1, VCAM-1, MMP-9in the culture supernatant were detected by ELISA method. Results 4-weekberberine treatment markedly reduced serum TC and LDL-c levels and improved the plaque stability in Apo-/-E mice fed with a high-fat diet(P＜0.05) which was comparable with the effect of atorvastatin. Berberine also significantly decreased the levels of IL-6 and TNF-α in mice serum and aortic tissues (P＜0.05). Berberine tended to decrease ALP, BMP-2 levels and the content of calcium in mice serum and aortic tissues (P＜0.05) which were not observed in atorvastatin group. Berberine significantly reduced the levels of ICAM-1, VCAM-1, and MMP-9 in TNF-α-stimulated HUVECs. Conclusions BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet, decrease the injury caused by inflammation, and attenuate vascular calcification. It may improve atherosclerosis and play a role in cardiovascular protection.

Key words: Key words: berberine, atherosclerosis, vascular endothelium, inflammation, vascular calcification