The Effect Of Atorvastatin And Probucol On Atherosclerosis In ApoE Gene Knock-out Mice

Objective:To study the combinational effects of atorvastatin and probucol on the atherosclerosis and the potential mechonism in Apo E-gene knockout mice. Methods:This study imitated the process of human atherosclerosis by feeding Apo E-knockout mice with high-fat diet. After 10 weeks' high-fat diet, the mice were given treatment intervention with atorvastatin(10 mg/kg/d) and 0.5% probucol. 27 Apo E-knockout mice were selected and randomly assigned to 5 groups:(1)control group, n=6, fed with the common diet and euthanized after 10 weeks;(2) model group, n=6, fed with high-fat diet and euthanized after 10 weeks;(3) blank group, n=5, fed with high-fat diet, were given pure water(0.3 ml/d) since 11 th week;(4)atorvastatin group, n=5, fed with high-fat diet, were given atorvastatin(10 mg/kg/d) since 11 th week;(5) combination group(atorvastatin + probucol), n=5, fed with high-fat diet, were given atorvastatin(10 mg/kg/d) and probucol in food since 11 th weeks. After 20 weeks(10 weeks' intervention), all the mice were sacrificed and blood sampled. Then detect the plasma lipid and ox-LDL. Artery was prepared for the morphologic study, the immunohistochemical analysis and the western blot analysis.Result: 1. There was no significant difference between the control and the model group in weight growth(P>0.05). There was also no significant difference among the 3 intervention groups in weight growth(P>0.05).2. Compared with the control group, the plasma TC, TG and ox-LDL level of model group were higher(P<0.05). The TC and the ox-LDL level in the atorvastatin and the combination group were lower than those in the blank group(P<0.05). The ox-LDL level in combination group were lower than that in the atorvastatin group(P<0.05).3. The atorvastatin group has lower ?-actin expression when compared with the blank group(P<0.05). Compared with the blank group, the atorvastatin and the combination group showed lower expression in lipid deposition, macrophages and higher ?-actin expression(P<0.05).4. The protein expression of MMP-9 and MCP-1 had difference among the 3 intervention groups(P<0.05). MMP-9 in the atorvastatin and the combination groups were less than that in the blank group(P<0.05), while there was no significant difference between that in the atorvastatin and the combination group(P>0.05). MCP-1 in the atorvastatin and the combination groups were less than that in the blank group(P<0.05), while there was no significant difference between that in the atorvastatin and the blank group(P>0.05).Conclusion: 1. Apo E-knockout mouse with high-fat diet can lead to the atherosclerosis in a short time and is a perfect model for atherosclerosis study.2. Atorvastatin can reduce the plasma TC and the ox-LDL level, which can be enhanced by combining with probucol.3. Atorvastatin can lead to an increase of vascular smooth muscle cell. Therefore, it has the anti-inflammation and anti-atherosclerosis effect. While combined with probucol, the vascular smooth muscle cell increased and the macrophages reduced at the same time.4. Atorvastatin shows a inhibition effect to the expression of MCP-1 and MMP-9. Whilst when it was used together with probucol, a much stronger inhibition effect was observed to the expression of MCP-1. Whilst no enhancement of the inhibition towards MMP-9 was observed.