Research On Rosuvastatin Intervening Progress Of Aortic Atherosclerotic Lesions In ApoE^-/- Mice

ObjectiveTo observe the influence of rosuvastatin on blood lipid level, inflammatoryfactors, cell factors and apoptosis related proteins in the process of atheroscleroticprogression of mice defected with apoE gene, and research on possible mechanisms ofresisting to atherosclerosis and potential drug targets of rosuvastatin.Methods20male mice defected in apoE gene were divided into model group andintervention (by rosuvastatin) group,10for each group, which were fed with high fatdiet, while10normal C57BL/6J mice were as control group, fed with normal diet.All mice were fed for13weeks, then blood lipid level of mice was tested by bloodbiochemical tests, and expression level of IL-6, hs CRP and Lp-PLA2was measuredby double antibody clip art in ELISA detection. Aortic tissue was taken to make HEdyed pathological slice for observation of aortic pathological changes in mice,TUNEL apoptosis kits was used to test aortic vascular cell apoptosis in mice,real-time fluorescent quantitative PCR was applied to detect mRNA expression levelof aortic MMP-9, VCAM1and MCP-1, Western blot method was used to detectthe Bcl-2and Caspase3expression in aortic blood vessels in mice. ResultsCompared with model group, level of TC, TG, LDL-C in mice defected in apoEgene in the intervention group was reduced, the difference was statistically significant(P <0.05). IL-6, hs CRP, Lp PLA2level of mice serum in intervention group arehigher than the control group, but except for the significant difference (P <0.01) inthe hs CRP level, the other two indicators had no statistically significant difference;Compared with model group, the level of IL-6, hs CRP, Lp-PLA2of mice serum inintervention group was significantly decreased, the difference was statisticallysignificant (P <0.05). Area of mice plaque within aorta endovascular in interventiongroup was larger than control group by observing aortic pathological findings, andless than model group, the difference was statistically significant (P <0.05).Apoptosis cells can be seen in blood vessels of mice in the intervention group throughTUNEL detection were significantly less than model group, and apoptotic cellsgathered in lipid core region under the fibrous cap of atheromatous plaque. Real-timefluorescent quantitative PCR detection found that compared with model group,mRNA expression of MCP-1-1, MMP-9and VCAM-1in aorta vascular inintervention group was relatively lower, the difference was statistically significant (P<0.05). Eesults of Western blot show that the expression of Bcl–2was highest inaorta vascular in the control group, then lower in intervention group, and lowest inmodel group; Expression of Caspase3was highest in model group, and the leastexpressed in normal group.ConclusionRosuvastatin not only can reduce the lipid levels of apoE gene defected mice, butalso can reduce the expression of systemic inflammatory response factor in micedefected in apoE gene, decrease cell apoptosis in aortic vascular in mice, reduceexpression of cytokines promoting atherosclerosis in blood vessels, restrain proteinexpression to promote apoptosis, increase the expression of protein resistant toapoptosis, as well as inhibit apoptosis within pathological endovascular to delay progression of atherosclerosis by reducing the inflammatory response.