The Effect Of Curcumin On Atherosclerotic Plaque And The Mechanisms Of Hepatic Lipid Metabolism In Apoe-/- Mice

Objective:1. To observe the effects of curcumin on the atherosclerotic plaque in apoE-/-mice;2. To study the expression of TNF-α、IL-6、Caveolin-1 and SREBP-2, explore the mechanism of curcumin on hepatic lipid metabolism in apoE-/-mice.Methods:The forty male ApoE-/- mice(from Peking University, China),18-20g, fed up with the chow diet for one week to adapt to the new environment, and then the mice were randomly divided into four groups:control group (0.5% CMCNa (0.2mL/10g/d)), model group (0.5% CMCNa (0.2mL/10g/d)), simvastatin group(5mg/kg/d) and curcumin (80mg/kg/d),gavaged every day. All the mice fed up with high-fat, high-cholesterol diet that contained 5.0% fat(wt/wt) and 1.0% cholesterol except for control group. Observed the statues of the mice,such as food intake and water intake.At the same time, recoded the weight of mice per week. After six week of treatment, collected the tissue specimens. And then the serum lipid(TC、TG、LDL-C、HDL-C) was detected by the Automatic biochemical analyzer; Assessment the Atherosclerotic plaque in aortic trees and aortic sinus by staining with oil red O; Observed the Atherosclerotic plaque in aortic arches by HE staining;The expression of TNF-aand IL-6 were measured by Elisa kit; And the expression of Caveolin-1、SREBP-2 in liver were detected by IHC and Western blot.Results:1. After the mice were administered with six weeks, body weight of model mice increased significantly, while the treatment groups can effectively reduce the growth trend. Detected by automatic biochemical analyzer, showed that the model group stimulated with high-fat diet, the content of serum TC, LDL-C was significantly increased, while the protective factor of HDL-C levels were significantly reduced. The treatment group fed up with curcumin can reduce the serum levels of TC and LDL-C.2. We observed the plaque area and plaque morphology in mice in the aortic arch and aortic sinus by paraffin and frozen sections. Compared with the control group of mice, the aortic plaque area of model mice increased significantly, there were large number of foam cells in plaque, thin fibrous cap, intimal thickening. The curcumin can reduce the plaque area of ApoE-/-mice in the aortic arch and aortic sinus;3. By taking pictures of liver tissue, the color of liver in control group was red vividly. compared with the control group, the liver of model mice is milky white and obvious graininess. Compared with the model group, the treatment groups’ were normal. Slice results showed that:compared with the control group, the lipid accumulation in liver cells, and local inflammation occurred; compared with the model group, the treatment group mouse’ hepatocytes morphology were normal, fewer lipids, fewer inflammation.4. By immunohistochemistry and Western blot, the results showed that curcumin can reduce the expression lever of TNF-α,IL-6 in liver, as well as the expression level of Caveolin-1 and SREBP-2.Conclusion:Curcumin can reduce the area of atherosclerotic plaque in ApoE-/- mice by lowering the lipid levels and reducing the accumulation of lipids in the liver, the potential mechanism may be related to inhibit the expression of proinflammatory cytokines TNF-α, IL-6 and the Caveolin-1/SREBP-2pathway in liver.