Therapeutic effect of rosuvastatin on atherosclerosis of apolipoprotein E (ApoE)-knockout mice and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective:To explore the influence of rosuvastatin in the lipid levels, atherosclerosis plaque and apoptosis in the plaque of atherosclerotic apolipoprotein E (ApoE)-knockout mouse models, and to clarify the mechanism of rosuvastatin in inhibiting atheromatous plaque and apoptosis in the plaque.Methods:Thirty healthy six-week old male mice were randomly divided into high fat diet group (n=10),rosuvastatin group (n=10)and general diet control group (n=10).The mice in first two groups were fed with high fat diet,and the mice in general diet control group were fed with general diet;4 weeks later the mice in three groups were respectively given 0.9% NaCl solution,rosuvastatin (10 mg·kg·d-1 )and 0.9% NaCl solution by gavage for 8 weeks.And then ELISA was used to detect the serum lipid levels,the area of atherosclerotic plaque was measured by HE staining, and the apoptosis in plaques was detected by TUNEL method;the expression of apoptosis-assoicated gene Bax protein was measured by immunohistochemical staining.Results:Compared with high fat diet group,the levels of total cholesterol (TC)and low density lipoprotein cholesterol (LDL-C)of the mice in rosuvastatin group were significantly decreased (P<0.05 or P<0.01),and the 1evel of high density lipoprotein cholesterol (HDL-C)was significantly increased (P<0.01).The aortic atherosclerotic plaque of the mice in high fat diet group was massive with a great quantity of foam cells, cholesterol crystal, necrotic cells and inflammatory cells in the plaque;the aortic atherosclerotic plaque of the mice in rosuvastatin group was smaller with less foam cells,necrotic cells and inflammatory cells;the aortic atherosclerotic plaque area of the mice in rosuvastatin group was significantly smaller than that in high fat diet group (P<0.01);the apoptotic index in the aortic atherosclerotic plaque of the mice in rosuvastatin group was significantly lower than that in high fat diet group (P<0.01).Compared with high fat diet group,the expression of Bax protein in rosuvastatin group was significantly decreased.Conclusion:Rosuvastatin may inhibit the progression of atherosclerotic plaque and the apoptosis in plaques through mitochondrial pathway.