胡椒碱抗ＡｐｏＥ^－／－小鼠动脉粥样硬化活性及作用机制

Aim To investigate the therapeutic effects of piperine (PIP) on atherosclerosis in ApoE mice fed with high fat diet and the potential mechanisms. Methods After PIP was administered for 20 weeks, aorta was stained by oil red O with the area of aortic plaque analyzed. The levels of blood lipids and serum inflammatory factors were detected. Hepatic expressions of oxidative stress related factors were determined. Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a series of concentrations of PIP after LPS induction. The levels of NO and oxidative lipids were detected and factors of PI3K/Akt/eNOS pathway were analyzed. Results Serum levels of TG, LDL-C, TNF-α and CRP were significantly reduced by PIP in ApoE^-/- mice compared with those in control group, whereas the level of HDL-C significantly increased. Besides, the percentage of aortic plaque area and the hepatic level of oxidative stress in ApoE^-/- mice also significantly decreased after the treatment of PIP. In addition, PIP significantly increased the content of NO and the SOD activity, while the level of lipid oxidation in HUVECs induced by LPS significantly decreased in the presence of PIP. Besides, PIP treatment induced the increase of Akt, eNOS and PI3K and the decrease of Bcl-2 and iNOS at gene and protein level. Conclusions Piperine effectively inhibits the occurrence and development of atherosclerosis in ApoE^-/- mice fed with high-fat diet, and the mechanism might be related to the regulation of PI3 K/Akt/eNOS signaling.