Atorvastatin reduces atherosclerosis in rabbits with hypercholesterolemia by inhibiting inflammatory response
10.3760/cma.j.issn.1673-4165.2014.05.006
- VernacularTitle:阿托伐他汀通过抑制炎症反应减轻高胆固醇血症兔动脉粥样硬化
- Author:
Yan HUANG
;
Guangxi ZHOU
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
Aorta;
Interleukin-10;
Interleukin-17;
Matrix Metalloproteinase 12;
Inflammation;
Hypercholesterolemia;
Rabbits
- From:
International Journal of Cerebrovascular Diseases
2014;22(5):381-386
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles of interleuldn (IL)-17,IL-10,and matrix metalloproteinase12 (MMP-12) in the pathogenesis of atherosclerosis and further to understand the intervention mechanism of atorvastatin for atherosclerosis.Methods Eighteen Japanese white rabbits were randomly divided into 3 groups:control,model and intervention groups (n =6 in each group).The control group,model group and intervention group were fed basic diet,high-fat diet,and high-fat diet plus atorvastatin (5 mg/(kg·d),respectively for 12 weeks.The levels of serum total cholesterol (TC) and triglyceride (TG) were determined by enzymatic colorimetric method; the levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by selective precipitation method; the levels of IL-17,IL-10,and MMP-12 were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA); the pathological morphology changes of atherosclerotic plaque was observe by HE staining; and the thickness of the intima,intima/media ratio,plaque area,and plaque proportion were calculated by image analysis software.Results The expression levels of serum TC,TG,LDL-C,and IL-17,as well as those of IL-17 and MMP-12 of the intervention group were significantly lower than those of the model group (all P ＜0.05),but they were still higher than the control group (all P ＜0.05),while there was no significant difference in the level of HDL-C.The level of serum IL-10 of the intervention group was higher than that of the model group and the control group (all P＜0.05).The thickness of intima,intima/media ratio,plaque area,and plaque proportion of the intervention group were all significantly lower than those of the model group (all P ＜0.05).Correlation analysis showed that the plaque proportion was significantly positively correlated with IL-17 (r =0.847,P =0.001) and MMP-12 (r =0.839,P =0.001),and was negatively correlated with IL-10 (r =0.794,P =0.002); IL-17 was significantly positively correlated with MMP-12 (r =0.709,P=0.001),and was significantly negatively correlated with IL-10 (r =0.738,P＜0.001).MMP-12 was significantly negatively correlated with IL-10 (r =0.563,P =0.015).Conclusion The increased levels of IL-17 and MMP-12,as well as the decreased level of IL-10 illustrate that inflammatory factors play an important pathological role in the pathogenesis of atherosclerosis.In addition to lipid-lowering effect,atorvastatin may decrease the degree of chronic arterial inflammatory response and play a role in anti-atherosclerosis by decreasing the expression of IL-17 and MMP-12,as well as increasing the expression of IL-10.
