Abstract: Objective  To explore the short-term effect of different doses of atorvastain on toll-like receptor 4 (TLR4) protein and TLR4-dependent downstream signaling monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-β (TGF-β) in an atherosclerotic rabbit model. Methods  A total of 28 New Zealand white rabbits were randomized into the normal group (n=6), model group (n=6), atorvastain low-dose group (n=8) and atorvastain high-dose group (n=8). Except for the normal group, the other groups were fed with 8-week high-fat diet combined with aortaventralis balloon-dilation injury to establish atherosclerotic model. After 8 weeks, the model group continued to eat high fat diet, while the two atorvastain groups received 2-week extra treatment with different doses of drug respectively. At the 10th week, all rabbits were sacrificed. Venous blood was drawn to measure serum lipid and ELISA was used to quantify the amount of inflammation mediators MCP-1 and TGF-β. HE, Masson and Sirius red staining were used to evaluate the amount of collagenous fiber and the pathophysiological changes of abdominal aorta. TLR4 was observed by immunohistochemical method. Results  At the end of the study, serum lipid and inflammation mediators MCP-1 and TGF-β in the normal group were significantly lower than those in the other three groups (P<0.05), and significantly lower in the two atorvastain groups than in the model group, while the decrease in the atorvastain high-dose group was much more obvious (P<0.01). The expression of TLR4 in the normal group was lower than those in the other three groups, which was significantly inhibited by high-dose atorvastain. Conclusion  Atorvastatin is able to lower serum lipid in a dose-dependent manner in short term, and decrease atherosclerosis by inhibiting TLR4 expression and regulating the downstream MCP-1 and TGF-β signaling pathways.

Key words: Toll-like receptor 4, Transforming growth factor-β, Atorvastatin, Monocyte chemoattractant protein-1, Atherosclerosis