Changes Of Inflammatory Factor On Atherosclerosis Of ApoE^-/- Mice And The Effect Of Drugs

ObjectiveAtherosclerosis is one of the commonest cardiovascular diseases,which brings great threaten to patients'health.In recent years,a lot of studies have showed that inflammation and immune mechanism take part in the pathophysi-ological process of atherosclerosis.Inflammatory factor play important roles in the course.The aim of this study is to observe expression of Thl/Th2 cytokines and resistin and evaluate the effect of rosuvastatin and ezetimibe intervence on atheroselerosis of apolipoprotein E knock-out mice.Our research would supply a new idea on investigate and cure of atheroselerosis.Methods48 four weeks old apoE-/- mice fed with high fat were divided randomly into four groups:model group, rosuvastatin calcium group(10mg/kg/d), rosuva-statin calcium group (5mg/kg/d), ezetimibe group.Mean while, take 12 healthy mice (C57BL/6 mice) with the same age and same genetic background to the normal group.Twelve weeks later, mice were anesthetized.Serum was saved. Concentrations of serum lipids (TC, TG, LDL and HDL) were measured by Biochemistry Analyzer.The excised aortic roots were examined for detailed histological analysis. Paraffin sections from the aortic root were stained with Hematoxylin and Eosin.The size of atherosclerotic lesion in each section was evaluated.Concentrations of IL-10, IFN-γin serum and the thoracoabdominal aorta and concentration of resistin in serum were measured by ELISA.Results1. AS emerged obviously in the aortic root in ApoE-/- mice fed with high fat diet, and the area of plaque was fairly large.2.Plasm TC and LDL were lower in rosuvastatin calcium groups and ezetimibe group than those in model group(P<0.05).3. Result of pathomorphology suggested that the pathological changes of ApoE-/- mice's aortas and coronary arteries in rosuvastatin calcium groups and ezetimibe group were obviously improved than model group, and the effect of rosuvastatin calcium group (10mg/kg/d) was better.4.The plaque areas of rosuvastatin calcium group (10mg/kg/d) were obviously smaller than that of model group(P<0.01).The plaque areas of rosuvastatin calcium group (5mg/kg/d) and ezetimibe group were smaller than that of model group(P<0.05). The plaque areas had significant difference among rosuvastatin calcium groups(P<0.05).5.The level of IFN-y in serum was elevated in model group compared to those with the Normal group(P<0.01).The level of IL-10 in serum was decreased in model group compared to those with the Normal group(P<0.05).The concentrations of IFN-y in serum were decreased in rosuvastatin calcium groups compared to those with model group(P<0.01).The concentrations of IL-10 in serum were elevated in rosuvastatin calcium groups compared to those with model group(P<0.01).The concentrations of IL-10 and IFN-y in serum had significant difference among rosuvastatin calcium groups(P<0.01).Difference in concentrations of IFN-y and IL-10 in serum between ezetimibe group and model group was not significant (P>0.05).6.The concentrations of IFN-y in the thoracoabdominal aorta were decreased in rosuvastatin calcium groups compared to those with model group(P<0.01). The concentrations of IL-10 in the thoracoabdominal aorta were elevated in rosuvastatin calcium groups compared to those with model group(P<0.01).The concentrations of IL-10 and IFN-y in the thoracoabdominal aorta had significant difference among rosuvastatin calcium groups(P<0.05). Difference in concentrations of IFN-y and IL-10 in the thoracoabdominal aorta between ezetimibe group and model group was not significant(P>0.05).7. The concentrations of Resistin in serum were elevated in model group compared to those with the normal group(P<0.01).The concentrations of Resistin in serum were decreased in rosuvastatin calcium groups compared to those with model group(P<0.01).The concentrations of resistin in serum had significant difference among rosuvastatin calcium groups(P<0.05).Difference in concentrations of resistin in serum between ezetimibe group and model group was not significant(P>0.05).Conclusions1.Apoe knock-out mice fed with high fat diet are good animal models for advanced atherosclerotic plaques research. The aortic root is a site where atatherosclerotic plaques have been reported to occur in the apoE knock-out mouse.Lesions develop rapidly at this site,especially under conditions of high fat diet.2.The content of Th1 cells related cytokines in serum and the thoracoabd-ominal aorta were increased,but Th2 cells related cytokines were decreased in the pathophysiological process of atherosclerosis.The imbalance between Th1 cells and Th2 cells may play an important role on the development of atherose-lerosis.3.Rosuvastatin could intervene with experimental atherosclerotic development in mice, which mechanism might be that rosuvastatin could supper-ssive lipid, and it could suppress the activation of Th1 related cytokines and improve the imbalance of Th1/Th2.4. The rosuvastatin calcium could significantly decrease the levels of IFN-γin serum and the thoracoabdominal aorta and decrease the levels of resistin in serum,inhibit inflammatory and inhibit the progression of atherosclerosis. Whereas rosuvastatin group(10mg/kg/d)has stronger influence than rosuvastatin group (5mg/kg/d).